3. Environmental Nutrion (Ch 9) Flashcards
1
Q
What estimates the burden imposed by envionmental dz, including those caused by communicable and nutritional dz?
A
global disease burgen GBD
2
Q
What is the sum of years of life LOST due to premature mortality and disability in a population?
A
Disability adjusted life year DALY
3
Q
in the GBD from 1990-2010 there was an increase in mortality due to HIV/AIDS which peaked in 2006. What is the leading global cause of health loss?
A
undernutrition
4
Q
Ischemic heart disease and cerebral vascular dz is the leading cause of death in developed countries. IN developed countries, 5 of 10 leading causes of death COD are?
A
infectious dz
5
Q
In the postnatal period, 50% of all deaths in kids less than 5 was attributed to 3 conditions which are all preventable, including?
A
penumonia
diarrheal dz
malaria
6
Q
Was there an increase or decrease in years of life lost in the following diseases?
Cadiovascular and Circulatory diseases
Cancer
neonatal conditions
Diarrhea, lower resp. infections, and other infectious dz
HIV/AIDS/ tuberculosis
A
INCREASED - Cadiovascular and Circulatory diseases
INCREASED- Cancer
DECREASED % life lost- neonatal conditions
DECREASED- Diarrhea, lower resp. infections, and other infectious dz
INCREASED- HIV/AIDS/ tuberculosis
7
Q
There are new emerging infectious diseases that are causing mortality due to many reasons such as HIV and what other two?
A
Multi-drug resistant Tb Dengue fever (climate change induced)
8
Q
CLimate change stands to become the preeminent global cause of environmental disease in the 21st century. Because of this, there are increasing incidence of disease such as malnutrition d/t disrupted crop, vector-borne dz such as malaria and dengue fever, and what other two things?
A
CV/Cerebrovascular/Resp dz d/t air pollution
Gastroenteritis/cholera/foodborne/waterborne dz- d/t contamination flood waters and disruption of clean water supplies
9
Q
Climate change leads to rising sea levels/ increased frequency of floods leads to contamination of water supplies which leads to?
A
increased gastrointestinal problems
10
Q
What is defined as the science of poisons, its studies distribution, effects, and mechanisms of action of toxic agents?
A
toxicology (radiation and heat)
11
Q
How many pounds of toxic chemicals including 72 million lbs of unrecognized carcinogens are released/year in the US?
A
4 BILLION
12
Q
What is strictly dependent on dosage- “all substances are poisons, the right dosage differentiates a poison from a remedy”?
A
Poison
13
Q
What are exogenous chemicals that are brought into the body through the skin, lungs and GI system (air water food) that are inherently toxic or are made toxic by metabolism (CYP450)?
A
Xenobiotics
14
Q
Most solvents and drugs are lipophilic, faciltating their transport and penetration through the basement memebrane. Solvents drugs and xenobiotics are metabolized to a inactive water soluble product (detoxification) or?
A
activated to form toxic metabolites
15
Q
In the liver is where xenobiotics get broken down in two phases… Phase 1: chemicals undergo hydrolysis, oxidations, or reduction which is done by CYP450. In phase 2 what occurs?
A
products of phase 1 reactions are converted into water soluble compounds (via glucuronidation, sulfation, methylation, and conjugation with glutathione) or into active compounds that cause cellular injury
16
Q
Both reactions in the liver via CYPs cause reactive oxygen species ROS as a byproduct. For example carbon tetrachloride to trichloromethyl free radical in the liver. What are some things that are metabolized by CYPS? 4
A
acetaminophen, barbiturates, warfarin, ETOH
17
Q
What decreases CYP activity?
A
fasting and starvation
18
Q
Airpolution is espicially hazardous to people with preexisting pulmonary or cardiac disease. Airborne microorganisms are the major cause of ?
A
morbidity and mortality
19
Q
Outdoor air pollution: EPA limits on sulfar dioxide, carbon monoxide, ozone, nitrogen dioxide, and what else?2
A
lead and particulate matter
smog = smoke + fog
20
Q
What outdoor pollutant is associated with the following…
Populations at risk: healthy adults and children / atheletes, outdoor workers, asthmatics
Effects: decreased lung function, increased airway reactivity, lung inflammation / decreased excercise capacity, increased hospitalizations
A
Ozone (O3)
21
Q
What outdoor pollutant is associated with the following…
Populations at Risk: healthy adults / individuals with chronic lung disease / asthmatics
Effects: increased airway reactivity / increased mortality / increased hospitalization and mortality
A
Sulfar Dioxide
22
Q
Ground level ozone toxicity is largely mediated free radicals, which injure respiratory tract epithlial cells and type 1 alveolar cells, releasing inflammatory mediators causing?
A
mild sx (decreased lung function and chest discomfort - more dangerous for people w asthma)
23
Q
What combines with ozone and particulate matter forming witches’ brew? Produced by power plants burning fossil fuels, copper smelting and paper mills… What sx can it lead to?
A
Sulfur dioxide
Sulfuric acid/sulfuric trioxide causes burning sensation in nose and throat, diffuculty breathing and asthma attacks
24
Q
What causes pulmonary inflammatoin and secondary cardiovascular effects due to inhalation of fine or ultrafine particles less than 10uM in diameter such as soot?
A
Paticulate matter
inhaled into alveoli, releasing inflammatory mediators** most harm here
25
What is nonirritating, colorless, tasteless, odorless gas produced when there is incomplete oxidation of hydrocarbons?
carbon monoxide
26
Acute CO toxicity occurs in a small room with car running - can induce coma or death in 5 minutes (or gas-generators in basment,etc). How does chronic poisoning occur?
working in tunnels, underground garages and in highway toll booths with high exposure to automobile fumes
27
CO kills by inducing CNS depression causing widespread ischemic changes which are particularly marked where? 2 (chronic) Is it reversible?
basal ganglia and lenticular nuclei
it is reversible but damage done will not reverse such as memory, vision, hearing and speech
28
Why does chronic poisoning to CO develop?
CO has a much higher affinity (200-fold) for hemoglobin than O2, so it replaces O2 causing generalized hypoxia = ischemia in CNS
29
What is characterized by generalized cherry red color of the skin and mucous membranes?
What is characterized by edematous brain, punctate hemorrhages and hypoxia-induced neuronal changes?
1. acute CO poisoning
| 2. rapid occuring death by CO- no morphological signs
30
Systemic hypoxia occurs when Hb is 20 to 30% saturated with CO, what percent is needed for death in under 5 minutes?
60-70% CO Hb saturation
31
Wood smoke contains polycyclic hydrocarbons which are carcinogens. Bioaerosols can cause infectious dz such as legionnaires, viral pneumonia, and are also caused by what?3
pet dander, fungi and molds
32
Radon is an environmental gas derived from uraniym which increases risk for lung cancer. Formaldehyde is used in building materials, and may be seen in poorly ventilated trailers after disasters, it is a carcinogen that can cause?
breathing difficulties, burning sensation in the eyes and throat and can trigger asthma attacks
33
What remains an elusive problem due to exposure to one or more indoor pollutants and poor ventilation?
Sick building syndrome
34
What metal is readily absorbed that binds to sulfhydryl groups in proteins and interferes with calcium metabolism, leading to hematologic, skeletal, neurologic, GI and renal toxicities?
LEAD
35
For children contamination was coming from flaking lead paint and soil. Some were exposed at their work, includding battery manufacturing, pigments tin cans and?
car radiators
36
Most of the absorbed lead is incorporated into bone and developing teeth - competing with calcium. What is its half life in bone?
20-30years
37
What kind of lead poisoning causes intellect, behavioral problems, hyperactivity, and poor organization skills in kids due to brain damage?
Low levels of lead poisoning
38
What kind of lead poisoning causes sensory motor and psychologic impairments, dec. IQ, learning diabilities, retarded development, blindness, siezure coma?
high levels of lead poisoning
39
NOTE: it is more uncommon for adults to get lead poisoning because children absorb 50% of lead while adults only absorb 15%. CNS disturbances=peripheral neuropathies are seen in adults with lead poisoning including?
extensor muscles of the wrist and fingers go first (wrist drop)
followed by paralysis of the peroneal muscles (foot drop)
40
Lead lines can be seen in the gums of adults with lead poisoning and can also be seen where?
radiodense lines in epiphyses/metaphyses in bone because lead interferes with remodeling of cartilage
41
Excess lead inhibits heme synthesis (ferrochelatase) which can lead to hypochromic microcytic anemia, basophilic stippling and what else?
ring sideroblasts- RBC with iron-laden mitochondria
42
The GI tract is a major source of clinical manifestations including what, which is characterized by extremely severe, poorly localized abdominal pain?
Lead colic
43
The kidney may form proximal tubule damage due to intranuclear inclusions of protein aggregates, chronic damage = interstitial fibrosis and possible?
renal failure
44
At a lead level in kids of about 10ug/mL, toxicity can be seen as decreased IQ levels, hearing, growth, impaired peripheral nerve function and fetal effects can be seen. What occurs at 40ug/mL?
decreased hemoglobin synthesis
45
In adults, lead poisoning is apparent by hypochromic microcytic anemia, red cell basophilic stippling, and demylination. How can one tell anemia and stippling via histo?
Hypochromic/microcytic anemia (MHC<80, MCH<27) can be seen as extremely small RBC when compaired to lets say a lymphocyte (will look huge)
Basophilic stippling when RBC becomes purple with dots!
46
What binds to sulfhydryl groups in certain proteins with high affinity and leads to damage in the CNS and the kidney?
Mercury
47
Main sources of mercury are contaminated fish, mercury vapors from dental amalgams. What disease is associated with cerebral palsy, deafness, blindness, mental retardation and major CNS defects in children exposed in utero?
Minamata disease
48
What interferes with cellular metabolism leading to toxicities that are most prominent in the gastrointestinal tract, nervours system, skin and heart?
Arsenic
49
Arsenic is in soil and water naturally - wood preservatives, herbicides, herbal medicines... Large quantities ingest, arsenic can cause acut GI, CV and what?
CNS toxicities that are fatal
50
2-8 weeks post exposure of arsenic you can see sensorimotor neuropathy, parathesias, numbness and pain. Chronic skin changes such as? 2
hyperpigmentation and hyperkeratosis
**chornic exposure can lead to increase risk for development of cancers of lung bladder and skin **palms and soles**
51
The most toxic form of arsenic is arsenic trioxide which is also a frontline treatment for?
acute promyelocytic leukemia
52
What is preferentially toxic to the kidneys and the lungs through uncertain mechanisms that may involve increased production of ROS?
Cadium - sources: nickel-cadium batteries, soil, plants = food
53
Along with cadium toxicity you will see obstructive lung disease, skeletal abnormalities d/y calcium loss and?
renal tubular damage which can lead to end stage renal dz
54
Cadmium-containing water used to irrigate rice fields in Japan and causes which disease in post-menopausal women that is a combination of osteoporosis and osteomalacia associated with renal disease?
Itai-itai ("ouch ouch") disease
55
What is demonstrated in workers exposed occupationally in populations living near zinc smelters?
Elevated risk for lung cancer
56
What are mees lines, which are white lines on the nails, a sign of?
Arsenic poisoning
57
Lung cancer can be caused by radon, asbestos, silica, bisether, nickel, arsenic, chromium, mustard gas or uranium. What is one major toxicant leading to leukemia and liver angiosarcoma?
Hematopoietic system-leukemia = benzene
| GI tract = Liver angiosarcoma = vinyl chloride
58
Fibrosis of the lungs is commonly caused by silica, asbestos, and cobalt... More than 10mil injuries at work occur per year, how many people die?
65,000 die of work related accidents and illnesses
59
Organic solvents such as _______&_______, are found in degreasing and dry cleaning agents and paint removers. Acute exposure to high levels can cause dizziness and confusion leading to CNS depression and coma.
chloroform and carbon tetrachloride
60
occupation exposure of rubber workers to benzene and 1,3butadiene increase the risk of leukemia. Benzene is oxidized by CYP2E1 to toxic metabolites in BM causing?
dose dependent marrow aplasia and acute myeloid leukemia (AML)
61
What are released during combustion of fossil fuels - coal and gas in tar and soot which leads to scrotal cancersin chimney sweeps?
Polycyclic hydrocarbons
62
Polycyclic hydrocarbons are among the most potent carcinogens and industrial exposures have been implicated in the development of?
lung and bladder cancer
63
What are synthestic lipophilic products that resist degredation, which are importantly used as PESTICIDES including DDT (dicholordiphenyltrichloroethane), non pesticide- PCBs (polychlorinated biphenyls) and dioxin?
Organochlorines
64
Organochlorines disrupt hormonal balance because of what two things?
antiestrogenic or antiandrogenic activity
65
What can cause skin disorders such as folliculitis and dermatosis known as chlorance characterized by acne, cyst formation, hyperpigmentation, and hyperkeratosis on the face and behind ears?
Dioxins and PCBs
66
Dioxins and PCBs also cause abnormalities of the CNS and liver. Who was poisoned with this?
president of ukraine viktor yushenko
67
Mineral dusts such as coal dust, silica, asbestos and beryllium can be inhaled and cause what?
pneumonconioses (chronic neoplastic lung dz)
68
Ferrugimous bodies - asbestos fibers coated in iron in the lungs... Asbetosis can be seen in workers and their family members and can cause what disease?
mesothelioma --- black lung
69
Exposure to vinyl chloride used in the synthesis of polyvinyl resins leads to the development of what, and uncommon type of hepatic tumor?
angiosarcoma of the liver ***** HY
70
What is used in the synthesis of polycarbonate food and water containers and of epoxy resins that line almost all food bottles and cans?
Bisphenol A (BPA)
71
Bisphenola A can cause heart disease in adult populations and in children who drink from BPA containers may have what?
potential endocrine effects
72
Tobacco is the leading exogenous cause of human cancer = 90% of lung cancers, causing 400,000 deaths a year. Tobacco decrases overall survival through?
dose-dependent effects expressed as pack years (#cig packs per day x # years smoking)
73
Cessation of smoking greatly reduces, within 5 years, overall mortality and the risk of death from CV disease. Lung cancer mortality decreases 21% within 5 years but?
excess risk of lung cancer persists for 30 years
74
There are more than 60 carcinogens identified in tobacco. Nicotine is not one and is not directly related to tobacco related disease but?
is strongly addictive
*binds to nicotinic receptors in brain and stimulates release of catcholamines from sympathetic neurons = inc heart rate/BP, cardiac output and contractility
75
```
The following of tobacco smoke are?
Tar
Polycyclic aromatic hydrocarbons
benzoapyrene
nitrosamine
```
Carcinogenic = cancer
76
Agents in smoke have a direct irritant effect on the tracheobronchial mucose causing inflammation and an increase in?
mucus production leading to bronchitis
77
Cigarette smoke causes the recruitment of leukocytes to the lung, causing increased elastase production and subsequent injury to lung tissue leading to?
emphysema
78
There is a 10fold higher incidence of lung carcinomas in asbestos workers and uranium miners who SMOKE. What is multiplicative interactions?
meaning if you smoke and drink you have an increased chance of laryngeal and oral cancers- with the more you do both the higher cancer of cancer
79
Cigarettes smoking is associated with cancers of the esophagus, pancreas, bladder, kidney, cervix and bone marrow.... The most common nonmalignant diseases caused by cigarette smoking include? 3
emphysema
chronic bronchitis
chronic obstructive pulmonary disease COPD
80
Cigarette smoking is strongly linked to the development of atherosclerosis and myocardial infarction. Multiplicative effects can be seen with what?
if patient is smoking and has hypertension and hypercholesterolemia
81
There is a 1.3 fold increase in lung cancer via passive smoke exposure / second hand /environmental tobacco smoke and what death is associated with second hand or passive smoke?
30-60k cardiac deaths yearly
*increased risk of asthma in children exposed in the home
82
maternal smoking increases the risk of spontaneous abortions, preterm births and?
intrauterine growth retardation IUGR
83
Despite all the attention given to illicit drugs, alcohol abuse causes more widespread hazard and claims many more lives. There are more than 10mil chronic alcholics in the US leading to how many deaths per year?
100,000 deaths annually
50% are d/t drunken driving, alcohol related homocides and suicide
15,000 per year due to cirrhosis of liver *** MCC death
84
Ethanol is absorbed unaltered in the stomach and SI and distributed to all tissues of the body in direct proportion to blood level. The amount exhaled is?
proportional to the blood level
* 80mg/dL in blood = legal def of drunk driving
- reached after 3 standard drinks
85
At what blood alcohol levels can one see drowsiness, stupor, and coma?
200mg/dL
300mg/dL
>300mg/dL = coma
86
Most of alcohol in the blood is oxidized to acetaldehyde in the liver via what enzyme?
alcohol dehydrogenase (ADH)
87
Acetaldehyde is converted to acetate by ADH, which is then utilized in the mitochondrial respiratory chain. EtOH can also induce CYP2E1 which can lead to what?
high alcohol can inhibit CYP2E1 which also processes other drugs- delaying drug catabolism, potentiating depressant effects of narcotic, sedative and other drugs
88
EtOH can be processed via peroxisomes in the liver via catalase, processed via CYP2E1 in microsomes/ER or processed in cytosol via alcohol dehydrogenase ADH... They all produce acetaldehyde which then goes where?
mitochondria and is processed via aldehyde dehydrogenase (ALDH) (when alcoholics increase in alch = increase in NADH and lactic acid leading to hepatic steatosis = fatty liver)
89
Acute alcoholism most affects the CNS (depressant) but also hepatic steatosis (fatty liver) and?
acute gastritis and ulceration
***all reversible if EtOH is discontinued
90
With chornic alcholism, there is a shortened life span due to damage of the liver, GI tract, CNS, cardiovascular system, and pancreas. What is mainly seen in the liver? 4
steatosis
alcholic hepatitis/cirrohsis
portal hypertension
increased risk for hepatocellular carcinoma
91
Chronic alcholism and the GI: will see massive bleeding from gastritis, gastric ulcers, esophageal varices (d/t cirrohsis). Thiamine (B1) deficiency is common in alcoholics, which presents as?5
```
peripheral neuropathies
wernicke-korsakoff syndrome (mamillary bodies gone)
cerebral atrophy
cerebellar degenerations
optic neuropathy
```
92
Alcoholic cardiomyopathy is dilated congestive cardiomyopathy, hypertension, and chronic alcohol consumption can cause liver injury leading to what?
a decrease in HDL production (good cholesterol) = inc risk coronary artery disease
93
Alcoholism also leads to acute and chronic pancreatitis. There is an increased risk of cancer in oral cavity, esophagus, liver and (breast ca in women) and lastly causing?
malnutrition and nutritional deficiencies (especially vit B)
94
One positive from alcohol is consuming moderate amounts (20-30gm/d) which is said to increase HDL, inhibit platelet aggreation and?
decrease fibrinogen levels possible protecting against CAD
*250mL wine/day
95
What syndrome is characterized by microcephaly, growth retardation, facial anomalies in a newborn, with decreased mental functions as child grows- first trimester is most harmful time?
Fetal alcohol syndrome
96
What are some of the facial abnormalities seen with fetal alcohol syndrome? 4
small palpebral fissures
low nasal bridge
NO PHILTRUM - smooth philtrum between upper lip and nose
epicanthic folds
97
What refers to untoward effects of drugs that are given in conventional therapeutic settings?
Adverse drug reactions
98
Drug induced hypersenstivity reactions most commonly present as skin rashes. What are two examples given?
discoloration of skin caused by minocycline
| drug metabolite/iron/melanin pigment particle deposition
99
Fatal adverse drug reactions are around 140,000 deaths per year... Two drugs that frequently cause adverse reactions are warfarin and dabigatran (inhibits thrombin)- can lead to bleeding and thrombosis due to insufficient dosage- what are these considered to be?
anticoagulants
100
Menopausal hormone therapy (MHT) was formerly known as hormone replacement therapy HRT consists of what?
administration of estrogens with progestogen
101
MHT was widely used in the past, until it was found that it did prevent fractures and osteoporosis, but it also lead to higher breast cancer, stoke, and venous thrombosis and had no affect on ?
incidence of coronary heart disease
dropped from 16 mil to 6 mil prescriptions in 2006 cause of scary news
102
Combination of estrogen-progestin increases risk of breast cancer, estrogen alone w hysterectomy = dec risk breast cancer. What did MHT show for heart incidences?
MHT has protective effect from development of atherosclerosis and CAD in women UNDER 60, no protection for women older than that
103
MHT increases risk of stroke and venous thromboembolism - including DVT. The increase in VTE is in the first 2 years in women with other risk factors like?
immobilizations and hypercoaguable states caused by prothrombin or factor 5 leiden
104
Oral contraceptives do no increase breast cancer risk. The do increase risk of cervical cancer especially when the patient is?
HPV+
| Note: decrease risk of ovarian and endometrial cancers
105
There is a 3-6X increase risk of venous thrombosis and pulmonary embolism in females using OCs, however there is NO increase risk of ?
CAD in women <30y/o BUT 2X increase in smokers >35y/o
106
What type of rare and benign tumor may show up due to an older patient with long term use of OCs?
hepatic adenoma
107
There are many adverse affects with anabolic steroids including stunted growth, acne, gynecomastia, testicular atropy, facial hair and menstrual changes in women and what otehr two things are common?
psychiatric issues and increase risk of MI
108
Acetaminophen is the most common analgesic used in the US. Toxicity is common in the US causing 50% of unintentional OD, 50% acute liver failures with what associated with this?
30% die ------ centrolobular necrosis
109
Acetominophen is detoxified from the system via phase II enzymes 95% of the time and is excreted in the urine as ?
glucoronate or sulfate conjugates
110
Phase I enzymes detoxify the other 5% **via CYP2E and produces a bad metabolite called NAPQI. It is normall conjugated to glutathione (**V important and needed so liver isnt damaged); when acetominphen levels are high what happens?
NAPQI accumulates and leads to centrilobular necrosis that may progress to liver failure by bringing proteins and depleting stores of glutathione
111
Injury via ______ occurs either via binding hepatic proteins causing damage or by making ROS and causing lipid peroxidation.
NAPQI
*toxicity can occur in lower amounts of acetominophen in alcoholics cause CYP2E is inhibited
112
Aspirin overdose - acute salicylate poisoning causes hyperventilation which leads to pure respiratory alkalosis, which is compensated by metabolic acidosis which allows diffusion of non-ionized salicylates into the brain, doing what?
effects the brain, causing nausea and coma.
113
Chronic aspirin/salicylism can develop in persons who take 3g or more daily for a long time. They present with HA, dizziness, tinnitus, bleeding, coma and what else? 2
```
analgesic nephropathy (tubulointerstitial nephritis with renal papillary necrosis)
acute erosive gastritis
```
114
```
The following are what class of drug?
Heroin
oxycodone
Methadone
Meperidine
```
Opioid Narcotics
115
```
The following are what class of drug?
Barbiturates
Ethanol
Methaquealone
Glutethimide
Ethchlorvynol
```
Sedative-hypnotics
116
```
The following are what class of drug?
Cocaine
Amphetamines
MMDA
Ecstasy (3-4-methylenedioxymethamphetamine)
```
Psychomotor stimulants
117
The following are what class of drug?
Phencyclidine (PCP/angel dust)
Ketamine
Phencyclidine like drugs
118
The following are what class of drug?
Marijuana
Hashish
Cannabinoids
119
The following are what class of drug?
Lysergic Acid Diethylamide (LSD)
Mescaline
Psilocybin
Hallucinogens
120
Cocaine inhibits reuptake of NT dopamine and norepinephrine in the central and peripheral nervous systems, initially causing euphoria, paranoia and hyperthermia. resulting in? 3
hypertension
tachycardia
peripheral vasoconstriction
121
Cocaine causes what by causing coronary artery vasconstriction and by enhancing platelet aggregation and thrombus formation?
Myocardial ischemia
122
Cocaine can asl precipitate lethal arrhythmias by enhanced sympathetic activity - not dose related. Can also cause CNS effects like hyperpyrexia and seizures. What happens if a preggers girl snorts coke?
it may cause acute decreased blood flow to the placenta resulting in fetal hypoxia and spontaneous abortion
123
What drug has clinical presentations of respiratory depression*, arrhythmia, cardiac arrest, and pulmonary edema?
opiates
*sudden death due to overdose
124
Along with opiates one can see increased infections, with 10% of the infections occuring where?
endocarditis of right heart valves
125
Lastly with opiates there are cutaneous lesions such as abscesses, cellulitis and ulcerations due to SubQ injections. What else with the liver and kidney is associated?
Viral hepatitis due to sharing needles
S. aureus infection MC (lungs)
amyloidosis and glomerulosclerosis of kidney
126
What drug known as speed or meth results in violent behavior, confusion, and psychotic symptoms such as paranoia and hallucinations?
Methamphetamine
127
MDMA or ecstasy cause euphoria and hallucinogen like feelings for 4-6 hours with increase in serotonin release. What are they usually spiked with?
like meth coke which enhance CNS effects
128
What increases heart rate and may or may not increase blood pressure which may causes angina in a pt with CAD. Also causes cognitive and psychomotor impairment with continued use--- ***large # carcinogens in smoke?
Marijuana
129
What is MRI detectable brain damage that ranges from mild to severe dementia?
Huffing/sniffing glue
| (bath salts=agitation/psychosis/mi/suicide
130
Burn injuries depend on depth of the burns, %body surface involved, internal injuries caused by inhalation of fumes, efficacy of therapy (fluid/electrolyte management + infection control). What is the greatest threat to life in burn patients on >20% of the body?(3)
shock
sepsis
respiratory insufficiency
131
What are the classifications of the following?
1st degree burn
2nd degree burn
3rd degree burn
1st degree burn: superificial and confined to the epidermis
2nd degree burn: partial thickness involving dermis
3rd degree burn: full thickness burn extending to the subcutaneous tissue and may go down to muscle
132
In burns greater than 20% of the body surface there is a rapid shift of body fluids into interstitial compartment leading to SHOCK. it is associated with generalized and pulmonary edema and also a?
hypermetabolic state associated with excess heat loss and an increase need for nutritional support
(the shift is due to systemic inflammatory response syndrome SIRS)
133
Along with shock and SIRS, there is also sepsis that may occur- virtually all burns colonized what 3 organisms?
pseudomonas aeruginosa
MRSA
Candida
134
The third thing seen with burns of body more than 20% is respiratory insufficiency within 24-48 hours, resulting from direct heat effects on mouth, nose and upper airways or from?
the inhalation of heated air and noxious gases in the smoke
*grafting has decreased organ failure largely
135
Full thickness burns are white/charred dry and painless because there is destruction of nerve endings, partial thickness are pink or mottled with blisters and painful. Devitalized tissues reveal?
coagulative necrosis, adjacent to vital tissue that quickly accumulates inflammatory cells and marked exudation
136
What is pugilistic stance?
burned beyond recognition, flexion of all joints and clenched fists
137
In heat stroke there is a lack of sweating, and the body temp rise more than 40 degrees because the thermoregulatory mechanisms fail. What is malignant hyperthermia?
heat stroke like rise in core body temp and muscle contractures in response to common anesthetics ***RYR1 gene mutation
138
What can usually be seen with malignant hyperthermia whos RYR1 gene is mutated?
hyperkalemia, tachycardia, arrhythmias, sustained muscle contractions (due to calcium leaking from cytoplasm)
139
Heat strokes are worse than heat exhaustion and you will have irreversible, multiorgan symptoms not seen in exhaustion. All because of?
forced inhibition of RYR1 gene under extreme conditions
140
What occurs when the body temp decreases under 90F causing loss of consciousness, bradycardia and then atrial fibrilation?
hypothermia
141
What injury has two types, including burns and ventricular fibrillation---- cardiac-respiratory failure and lightening classic high voltage injury (called lichtenberg figures via lightening strike)?
electrical injury
142
Ionizing radiation can remove tightly bound electrons which are able to collide into electrons and create and electron cascade known as?
an ionization
143
Main sources of ionizing radiation are x rays and gamma rays, high energy neutrons & alpha/beta particles. Ionization causes fibrosis in many places in the body and can also cause? 3
mutagenesis
carinogenesis
teratogenesis
144
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Radiation units: match each
-radiation emitted
-energy absorbed
-the equivalent dose = ( to the absorbed dose multiplied by the relative biologic effectiveness of the radiation)
A. Gray (Gy)
B. Sievert (SV)
C. Curie (Ci)
```
Curie (Ci)-radiation emitted
Gray (Gy)-energy absorbed
Sievert (SV)-the equivalent dose = (the absorbed dose multiplied by the relative biologic effectiveness of the radiation)
145
What are the following?
1. Rate of delivery
2. Field Size
3. Cell proliferation
4. O2 effects and hypoxia
5. Vascular damage
Main determinants regarding the biologic effects of ionizing radiation
146
What tissues are extremely vulnerable to radiation because they have a high rate of cell division? 4
gonads
BM
Lymphoid Tissue
Mucosa of GI tract
147
Ionizing radiation has a direct and indirect effect. The direct effect is to cause DNA damage leading to either repair or failed repair--> Cell death, Teratogenesis, or carinogenesis (if transforming events occur). What is important of the indirect effect?
The indirect effect causes free radical formation which is enhanced at high oxygen tension *** main way DNA damage occurs
148
Ionizing radiation causes changes in chromosomes related to double stranded breaks- deletions, translocations, and fragmentations. What 5 things are seen morphologically?
nuclear swelling
giant cells w/ pleomorphic nuclei (different)
>1 nucleus may be seen
cytoplasmic swelling
149
Endothelial cell proliferation, collagenous hyalinization and thickening of the intima are seen in irradiated vessels resulting in ?
marked narrowing or obliteration of the vascular lumen
150
Histologic constellation of cellular pleomorphism, giant cell formation, conformational changes in nuclei, and abnormal mitotic figures creates a more than passing similarity between?
radiation-injured cells and cancer cells
**plagues pathologists when evaluating irradiated tissue to look for cancer*
151
What can happen to the vessels if radiation hits them?
radiation induced chronic vascular injury with subintimal fibrosis occluding the lumen
152
Total body irradiation can be devastating if the dose is over 1Sv. If it is over 1SV is can cause health effects known as acute radiation syndromes which involve what main organs? 3
hematopoietic, gastrointestinal, and central nervous systems
| as dose gets higher and higher
153
Acute effects on hematopoietic and lymphoid systems at high doses and large exposure fields can kill lymph nodes directly. Dose dependent _______ can occur because hematopoietic precursors in the BM are susceptible.
marrow aplasia - can recover if the radiation is removed
154
With radiation, there is a rise in neutrophil and then neutropenia all the way down to zero. What other two things are common in acute effects of radiation on BM?
thrombocytopenia and anemia
*Extremely high doses kills BM stem cells and causes permanent aplastic anemia
155
With exposure to radiation, there is an increase incidence of leukemias and solid tumors (hiroshima), increased thyroid cancers in survivors of chernobyl. What increases in inhabitants of marshall islands exposed to nuclear fallout?
thyroid tumors
| increase frequency of leukemias and birth defects
156
Second cancers such as acute myeloid leukemia, myelodysplastic syndrome and solid tumors in individuals who received?
radiation for hodgkin lymphoma
157
Dose: 0.15
Organ: Testes
Health Effect: ?
Temporary Sterility
158
Dose: 0.50
Organ: Bone marrow
Health Effect: ?
depression of hematopoeisis
159
Dose: 1-2
Organ: Skin
Health Effect: ?
Reversible skin effects (erythema)
160
Dose: 2.5-6
Organ: Ovaries
Health Effect: ?
Permanent Sterility
161
Dose: 3-5
Organ: Skin
Health Effect: ?
Temporary hair loss
162
Dose: 3.5
Organ: Testes
Health Effect: ?
Permanent Sterility
163
Dose: 5
Organ: Lens of eye
Health Effect: ?
Cataract
164
```
Total-Body Ionization
Amount Sv: 1-2 Sv
Site of Injury: Lymphocytes
Main signs/sx: 2
Time development: 1 day to 1 week
Lethality: None
```
Sx: moderate granulocytopenia
| lymphopenia
165
```
Total-Body Ionization
Amount Sv: 2-10Sv
Site of Injury: Bone Marrow
Main signs/sx: 4
Time development: 2-6 weeks
Lethality: Variable 0-80%
```
Sx: leukopenia, hemorrhage, hair loss, vomiting
166
```
Total-Body Ionization
Amount Sv: 10-20Sv
Site of Injury: Small Bowel
Main signs/sx: 4
Time development: 5-14 days
Lethality: 100%
```
Sx: diarrhea, fever, electrolyte imbalance, vomiting
167
```
Total-Body Ionization
Amount Sv: >50Sv
Site of Injury: Brain
Main signs/sx: 4
Time development: 1-4 hours
Lethality: 100%
```
Sx: ataxia, coma, convulsions, vomiting
168
There is early damage to blood and bone marrow via radiation including lymphopenia, granulocytopenia and what other 2 things?
thrombocytopenia
| anemia
169
There is early damage to gonads via radiation including testes destruction (spermatogonia, spermatid, sperm), ovarie destruction (germ cells, granulosa cells) and what else?
Atrophy and fibrosis of gonads (late cause)
170
Radiation damage is done to the GI tract and presents as mucosal injury, ulceration and?
fibrosis of wall (late)
171
Radiation damage to lymph nodes leads to acute tissue loss and what, late changes?
atropy and fibrosis
172
Radiation damage to the lungs can cause edema, ARDS (acute respiratory distress syndrome), and?
interstitial fibrosis (months to years later)
173
Radiation to the skin can cause early erythema and edema, and later on dyspigmentation and?
atrophy / cancer (months to years later)
174
Radiation to adult brain is resisitant to damage but an embryonic brain will experience?
destruction of neurons and glial cells
175
Fibrosis, vascular changes and fibrointimal thickening w/ arteriolar sclerosis can be seen in what, which is produced by radiation therapy of the neck region?
Salivary glands
176
Chronic radiation dermatitis with atrophy of the epidermis and dermal fibrosis may be seen along with what else histologically?
telangiectasias and or subcutaneous blood vessels
177
After extensive radiation to the lung for carcinoma, you can see a fibrosed/thickened pericardial sac along with?
extensive mediastinal fibrosis
178
Malnutrition aka protein energy malnutrition (PEM) is the consequence of inadequate intake of proteins and calories, or deficiencies in the digestion or absorption of proteins leading to?
loss of fat and muscle tissue, weight loss, lethargy and generalized weakness
(obesity leads to diabetes, athersclerosis, cancer)
179
Dietary insufficiency = primary = missing from diet. secondary insufficiency is due to?
malabsorption, impaired utilization or storage, excess loss or increased need
180
Poverty, infections, acute and chronic illness, chronic alcoholism, ignorance and failure of diet supplementation and what else is a cause of dietary insufficiency?
self-imposed dietary restirctions, GI diseases, and malabsorption symptoms
181
What occurs in 50% of deaths in infacncy and childhood in developing countries AND older and debilitated patients in nursing homes and hospitals?
protein-energy malnutrition (PEM)
182
It is estimated that more than 50% of older reisdents in nursing homes in the US are malnourished, Weight loss of more than 5% is associated with PEM leading to?
PEM increases mortality in nursing home patients by 5 fold
183
What includes 1) depletion of subcutanteous fat in arms, chest wall, shoulder or metacarpal regions 2) easting of the quadriceps and deltoid muscles 3) ankle or sacral edema?
signs of secondary PEM
184
A child is considered to have what, when weight falls to 60% of normal for sex height and age? Child will suffer from growth retardation and muscle loss.
Marasmus
185
In children with marasmus, they have anemia and immune deficiency and muscle proteins and subcutaneous fat is used as fuel causes EMACIATED extremities... What is normal in these children?
they have normal serum albumin (head much larger than deteriorating body)
186
A child is considered to have what when protein deprivation is relatively more severe than the deficit in total calories?
Kwashiorkor
187
With kwashiorkor, there is depletion of visceral protein compartment with enlarged fatty liver- sparing subcutaneous fat and muscle. Present with chronic diarrhea, nephrotic syndrome, extensive burns. What is the most important aspect of this malnutrition?
There is hypoalbuminemia causing generalized EDEMA along with vitamin deficiency, immune deficiency and secondary infections
188
PEM is common complication in patients with AIDS or advanced cancers and in these settings it is known as?
cachexia
189
Cachexia occurs in 50% of cancer patients, most commonly GI, pancreatic, and lung cancers. You can see extreme weight loss, fatigue, muscle atrophy, anemia, anorexia and edema. Mortality is commonly from?
atrophy of the diaphragm and other respiratory muscles
190
Cachexia is possibly caused by mediators from the cancer or tumor such as proteolysis - inducing factor and lipid-mobilizing factor which increases FA oxidation via which cytokine?
TNF** / IL6
191
proteolysis - inducing factor PIF and proinflammatory cytokines (TNF) from tumors cause skeletal muscle breakdown through which pathway?
NFkB induced activation of upiquitin proteasome pathway which promotes degredation of skeletal muscle structural proteins such as myosin heavy chain by upregulating expression of several muscle specific ubiquitin ligases - which are tagged and then degrated by proteasomes
192
The main anatomic changes in PEM are growth failure and peripheral edema (kwashiorkor) and loss of body fat and atrophy of muscle (marusmus). Liver is enlarged and fatty in ______?
kwashiorkor- along with small bowel atropy
*brain and BM hypoplastic
193
What is defined as self induced starvation resultin in marked weightloss?
anorexia nervosa
194
What is a condition in which the patient binges on food and then induces vomiting?
Bulimia
195
In what eating disorder can you see severe PEM like clinical features, along with amenorrhea** diagnostic, decrased thryoid hormone and decreased bone density?
Anorexia nervosa
*major complication is an increased susceptibility to cardiac arrhythmia and sudden death from hypokalemia (also with bulimia)
196
In bulimia, less than 50% have amenorrhea, they have a better prognosis than aneroxics. Major complication are from vomiting/diarrhea including 1)electrolyte imbalance (hypokalemia) and what other two things?
2) pulmonary aspiration of gastric contents
| 3) esophageal and gastric rupture
197
What can be seen if someone is deficient in vitamin K?
bleeding diathesis
198
What can be seen if someone is deificient in vitamin B1 - thiamine? 3
dry and wet beriberi
wernike syndrome
korsakoff syndrome
199
What can be seen if someone is deficient in vitamin B3 - niacin? 3
Pellagra = 3Ds = dementia, dermatitis, diarrhea
200
What can be seen if someone is deficient in vitamin B6 (pyroxidine)? 5
```
cheilosis
glossitis
dermatitis
peripheral neuropathy
maintenance of myelinization of SC tracts
```
201
What clincial features can be seen if someone is deficient in zinc? 7
Rash around eyes, mouth, nose, and anus called acrodermatitis enteropathica
202
What clincial features can be seen if someone is deficient in iron? 1
hypochromic microcytic anemia
203
What clincial features can be seen if someone is deficient in Iodine? 1
Goiter and hypothyroidism
204
What clincial features can be seen if someone is deficient in copper? 3
muscle weakness
neurologic defects
abnormal collagen cross linking
205
What clincial features can be seen if someone is deficient in Fluroide? 1
Dental caries/cavities
206
What clincial features can be seen if someone is deficient in selenium? 2
myopathy
| cardiomyopathy (keshan disease)
207
Vitamin A known as retinol, retinal, and retinoic acid functions in the maintenance of normal vision, regulation of cell growth and differentiation and regulation of lipid metabolism. Secondary deficiency in vit A is due to fat malabsorption as seen in?
celiac, crohn, colitis, CF*, and bariatric surgery
208
Vitamin A can cause immune deficiency, increasing mortality rates from common infections. Night blindness is commonly seen as well as what?
epithelial squamous metaplasia (such as in respiratory epithelial-leading to inc. pulmonary infections) and keratinization
209
In the eye one can seen xeropthalmia (dry eyes), keratomalacia (corneal destruction) and what else?
BITOT spots - build up of keratin debris which erodes causing keratomalacia
210
Acute VIt A toxicity presents with headache, dizziness, V, stupor and blurred vision, and confused with pseudotumor cerebri. What about in chronic toxicity?
weight loss, anorexia, N&V, bone and joint pain
211
Vitamin A is a fat soluble VIT, requiring bile, pancreatic enzymes and some antioxidant activity in the food. Retinol (B-carotene) is absorbed in the intestine, which is transported in chylomicrons to the liver via?
APOE
212
Once absorbed in the liver, 90% is stored in the perisinusoidal steallate cells, which provide Vit A for 6 months. Upon release retinol binds to?
retinol binding protein RBP and is mobilized to the tissues- where it binds a cellular RBP
213
Once retinol is bound to cellular RBP in the tissues, the RBP is released back into the blood. Retinol may be stored in tissues as retinyl ester or?
oxidized to retinoic acid for epithelial differentiation and growth
214
What vitamin has a major function of maintaining adequate plasma levels of calcium and phosphorus to support metabolic functions, bone mineralization and neuromuscular transmission?
Vitamin D
215
Vitamin D is needed for prevention of rickets (children whose epiphysis arent closed), osteomalacia (adults form rickets) and?
hypocalcemic tetany (state caused by an insufficient extracellular concentration of ionized calcium - needed for relxation of muscles)
216
What form of vitamin A induces the differentiation and subsequent apoptosis of acute promyelocytic leukemia cells through its ability to bind to the PML-RARα fusion protein that characterizes this form of cancer?
all-trans-retinoic acid
217
With what disease or malnutrition can one see frontal bossing, squared head, rachitic rosary (ribs bending), pigeon breast deformity, lumbar lordosis and BOWing of the legs?
Rickets
218
Vitamin D was recently found to help clear MTb infections in patients. In osteomalacia, what can be seen?
inadequate minzeralization of bone, weak and prone to fracture (excess of persistent osteoid)
219
The major source of vitamin D for humans is its exogenous synthesis from a precursor, 7-dehydrocholesterol in a photochemical reaction that requires ?
sun or artificial UV light in the range of 290-315nm
220
Vitamin D metabolism:
1. photochemical synthesis of D from 7-dehydrocholesterol and abosrption of D from food and supplements in the gut
2. D binds plasma a-globulin (DBP) and transports to liver
3. COnversion of D to 25OHD in liver and through action of 25-hydroxylase (CYP27A1)
4. Conversion of 25OHD to 125OH2D3 the most active form of vitamin D via 1a-hydroxylase in kidney- this production is regulated by what three mechanisms?
1. hypocalcemia stimulates secretion of parathyroid hormone -> 1ahydroxylase
2. hypophosphatemia activates 1ahydroxylase
3. feedback mech in which increase in levels of 125OH2D3 down regulates itself by inhibiting 1ahydroxylase
221
Vitamin D has many roles, including stimulation of instestinal calcium absorption, stimulation of calcium reabsorption in the kidney, interaction with PTH in the regulation of blood caclium and?
mineralization of bone
222
In vitamin D deficiency, there is adequate substrate for the renal 1-a-hydroxylase, causing deficiency in 125OH2D leading to?
decrease Ca and P absorption in the gut
223
decrease Ca and P absorption in the gut leads to depressed serum levels of both. Hypocalcemia activates parathyroid glands causing?
mobilization of calcium aand phosphorus from bone
224
mobilization of calcium aand phosphorus from bone occurs due to PTH, and simultaneously PTH induces wasting of phosphate in urine and calcium retention, resulting in what levels?
Ca is near normal
Phosphate is low
mineralization is impaired (bone)
225
With rickets upon histology, you can compare costochondral junction with normal child. In normal you see formation of cartilage palisades and orderly transition from cartilage to new bone. What can be seen in rickets bbs?
rachitic costochondral junction in which the palisades of carilage is LOST w pale trabeculae = uncalcified osteoid (dark purkle = well formed bone)
226
What is caused by megadoses of orally taken vitamins which in children cause metastatic calficications of soft tissue (kidney) and in adults causes bone pain and hypercalcemia?
Vitamin D toxicity
227
A deficiency of what leads to development of scurvy, characterized by bone disease in growing children and by hemorrhages and healing defects in children and adults?
water soluble Vitamin C deficiency
228
Vitamin C functions as an antioxidant as well in the activation of prolyl and lysyl hydroxylases from inactive precursors providing hydroxylation of procollagen (corsslink collagen fibers). It is not synthesized in humans so?
we are entirely dependent on Vit C in our diets
| milk, liver, fish, fruits, vegies
229
Primary deficiencies of Vit C are from diet and secondary def. is commonly seen in older individuals who live alone and in?
chronic alcoholics - groups that often have erratic and inadequate eating patterns
230
Sometimes scruvy is seen in food faddists, and in patients undergoing peritoneal dialysis and?
hemodialysis
231
When there is vitamin deficiency, there is impaire collagen formation leading to poor vessel support resulting in bleeding tendancies, as well as what two other things?
inadequate synthesis of osteoid
| impaired wound healing
232
Excess vitamin C is associated with iron overload, hemolytic anemia in those w G6PD deficiency and?
calcium oxalate kidney stones
233
NOTE: kwashiorkor is a diet with normal calories but lacking protein and marusmus is?
a diet with low/no protein and or calories
234
Listen the following BMI categories:
18.5-25kg/m2
25-30 kg/m2
>30kg/m2
18.5-25kg/m2 : normal
25-30 kg/m2 : overweight
>30kg/m2 : obese
235
Obesity is an accumulation of adipose tissue that is of sufficient magnitude to impair health. Excess adiposity and body weight is associated with increase incidence of what?5
```
Type 2 DM
Dyslipidemias
Cardiovascular dz
HTN
Cancer
```
236
What is it called when fat accumulates in the trunk and abominal cavity, associated with an increased risk for several diseases, more than excess accumulation of fat diffusely in subQ tissue?
Central or visceral obesity
237
The peripheral afferent system of neurohumoral mechanisms, that regulate energy balance, generates signals from various sites, its mains components are? 5
leptin and adiponectin produced by fat cells
Ghrelin from the stomach
Peptide YY PYY from the ileum and colon
Insulin from the pancreas
238
Leptin increases energy consumption and inhibits food intake (adipose)
PYY inhibits foot intake (intestines)
What does grehlin do?
from the stomach, increases food uptake ** only one
239
In addition to leptin and adiponectin, adipose tissue (adipocytes) produces cytokines such as TNF , IL6, IL1, IL18, chemokines and steroid hormones. What does this lead to?
a chronic proinflammatory state marked by high levels of circulating Creactive protein.
***Note: the proinflammatory state associated with obesity may be carcinogenic
240
Obesity is the main driver of a cluster of alterations known as metabolic syndrome which is?
visceral or intraabdominal adiposity, insulin resistance, hyperinsulinemia, glucose intolerance, HTN, hypertriglyceridemia and low HDL
241
Obese persons generally have hypertriglyceridemia and low HDL both of which incrase the risk of?
Coronary artery disease
242
Obesity is also associated with nonalcoholic fatty liver disease. What occurs 6X greater in obese than in lean people?
cholelithiasis (GALLSTONES)
243
Obesity is associated with hypoventilation syndrome called pickwickian syndrome. What can happen both at night and day, which is often associated with sleep apnea, polycythemia and right sided heart failure (cor pulmonale)?
Hypersomnolence (excessive sleepiness)
| also seen is osteoarthritis d/t excessive weight bearing
244
In 2007, national cancer institute estimated that 4% of cancers in men and 7% of cancers in women were attributed to obesity. There is an increased risk for cancers of esophagus, pancreas, colon, rectum, breast, endometrium, and what other three?
kidney, thryoid, gallbladder
245
Insulin resistance leads to hyperinsulinemia which has multiple effects that may directly or indirectly contribute to cancer, such as?
Hyperinsulinemia increases free insulin growth factor 1 (IGF1), IGF1 is a mitogen which binds high affinity to its receptor which is expressed in many cancers, activating RAS and PI3K/AKT pathways for growth
246
Excess body weight and Type II DM/Metabolic syndrome lead to insulin resistance and HYPERINSULINEMIA**BAD**. Hyperinsulinemia causes decrease in adiponectin and IGFBP1 which leads to?
large increase in IGF1 causing cell proliferation increase and apoptosis decrease in the target cell (contribute to tumor development)
247
With respect to carinogenesis, three aspects of the diet are of major concern including 1) content of exogenous carcinogens 2) endogenous synthesis of carinogens from dietary compounds and ?
3) lack of protective factors
248
Exogenous substances like ______ is involved in development of hepatocellular carinomas.
aflatoxin
249
Synthesis of endogenous carcinogens like _____ and _____ lead to gastric carcinomas.
Nitrosamines and nitrosamides
250
High animal fat intake combined with low fiber intake has been implicated in the casusation of?
colon cancer
| total dietary fat has a +correlation with Breast cancer
251
Vitamins C and E, B-carotenes (retinol precursor), and selenium seem to have what kind of effects due to antioxidant properties?
anticarinogenic!
252
The central question is can dietary modification --specifically reduction in consumption of cholesterol and saturated animal fats (egg/butter/beef)-- reduce serum cholesterol levels and prevent or retard the development of athersclerosis and most importantly?
CAD
Note: recent studies have shown omega-3 fatty acid supplements do not lower the risk of CV disease
