3. Environmental Nutrion (Ch 9) Flashcards
What estimates the burden imposed by envionmental dz, including those caused by communicable and nutritional dz?
global disease burgen GBD
What is the sum of years of life LOST due to premature mortality and disability in a population?
Disability adjusted life year DALY
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?
undernutrition
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?
infectious dz
In the postnatal period, 50% of all deaths in kids less than 5 was attributed to 3 conditions which are all preventable, including?
penumonia
diarrheal dz
malaria
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
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
There are new emerging infectious diseases that are causing mortality due to many reasons such as HIV and what other two?
Multi-drug resistant Tb Dengue fever (climate change induced)
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?
CV/Cerebrovascular/Resp dz d/t air pollution
Gastroenteritis/cholera/foodborne/waterborne dz- d/t contamination flood waters and disruption of clean water supplies
Climate change leads to rising sea levels/ increased frequency of floods leads to contamination of water supplies which leads to?
increased gastrointestinal problems
What is defined as the science of poisons, its studies distribution, effects, and mechanisms of action of toxic agents?
toxicology (radiation and heat)
How many pounds of toxic chemicals including 72 million lbs of unrecognized carcinogens are released/year in the US?
4 BILLION
What is strictly dependent on dosage- “all substances are poisons, the right dosage differentiates a poison from a remedy”?
Poison
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)?
Xenobiotics
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?
activated to form toxic metabolites
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?
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
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
acetaminophen, barbiturates, warfarin, ETOH
What decreases CYP activity?
fasting and starvation
Airpolution is espicially hazardous to people with preexisting pulmonary or cardiac disease. Airborne microorganisms are the major cause of ?
morbidity and mortality
Outdoor air pollution: EPA limits on sulfar dioxide, carbon monoxide, ozone, nitrogen dioxide, and what else?2
lead and particulate matter
smog = smoke + fog
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
Ozone (O3)
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
Sulfar Dioxide
Ground level ozone toxicity is largely mediated free radicals, which injure respiratory tract epithlial cells and type 1 alveolar cells, releasing inflammatory mediators causing?
mild sx (decreased lung function and chest discomfort - more dangerous for people w asthma)
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?
Sulfur dioxide
Sulfuric acid/sulfuric trioxide causes burning sensation in nose and throat, diffuculty breathing and asthma attacks
What causes pulmonary inflammatoin and secondary cardiovascular effects due to inhalation of fine or ultrafine particles less than 10uM in diameter such as soot?
Paticulate matter
inhaled into alveoli, releasing inflammatory mediators** most harm here
What is nonirritating, colorless, tasteless, odorless gas produced when there is incomplete oxidation of hydrocarbons?
carbon monoxide
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
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
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
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?
- acute CO poisoning
2. rapid occuring death by CO- no morphological signs
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
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
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
What remains an elusive problem due to exposure to one or more indoor pollutants and poor ventilation?
Sick building syndrome
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
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
Most of the absorbed lead is incorporated into bone and developing teeth - competing with calcium. What is its half life in bone?
20-30years
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
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
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)
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
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
The GI tract is a major source of clinical manifestations including what, which is characterized by extremely severe, poorly localized abdominal pain?
Lead colic
The kidney may form proximal tubule damage due to intranuclear inclusions of protein aggregates, chronic damage = interstitial fibrosis and possible?
renal failure
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
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!
What binds to sulfhydryl groups in certain proteins with high affinity and leads to damage in the CNS and the kidney?
Mercury
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
What interferes with cellular metabolism leading to toxicities that are most prominent in the gastrointestinal tract, nervours system, skin and heart?
Arsenic
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
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
The most toxic form of arsenic is arsenic trioxide which is also a frontline treatment for?
acute promyelocytic leukemia
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
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
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
What is demonstrated in workers exposed occupationally in populations living near zinc smelters?
Elevated risk for lung cancer
What are mees lines, which are white lines on the nails, a sign of?
Arsenic poisoning
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
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
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
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)
What are released during combustion of fossil fuels - coal and gas in tar and soot which leads to scrotal cancersin chimney sweeps?
Polycyclic hydrocarbons
Polycyclic hydrocarbons are among the most potent carcinogens and industrial exposures have been implicated in the development of?
lung and bladder cancer
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
Organochlorines disrupt hormonal balance because of what two things?
antiestrogenic or antiandrogenic activity
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
Dioxins and PCBs also cause abnormalities of the CNS and liver. Who was poisoned with this?
president of ukraine viktor yushenko
Mineral dusts such as coal dust, silica, asbestos and beryllium can be inhaled and cause what?
pneumonconioses (chronic neoplastic lung dz)
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
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
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)
Bisphenola A can cause heart disease in adult populations and in children who drink from BPA containers may have what?
potential endocrine effects
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)
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
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
The following of tobacco smoke are? Tar Polycyclic aromatic hydrocarbons benzoapyrene nitrosamine
Carcinogenic = cancer
Agents in smoke have a direct irritant effect on the tracheobronchial mucose causing inflammation and an increase in?
mucus production leading to bronchitis
Cigarette smoke causes the recruitment of leukocytes to the lung, causing increased elastase production and subsequent injury to lung tissue leading to?
emphysema
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
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
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
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
maternal smoking increases the risk of spontaneous abortions, preterm births and?
intrauterine growth retardation IUGR
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
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
At what blood alcohol levels can one see drowsiness, stupor, and coma?
200mg/dL
300mg/dL
>300mg/dL = coma
Most of alcohol in the blood is oxidized to acetaldehyde in the liver via what enzyme?
alcohol dehydrogenase (ADH)
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
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)
Acute alcoholism most affects the CNS (depressant) but also hepatic steatosis (fatty liver) and?
acute gastritis and ulceration
***all reversible if EtOH is discontinued
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
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
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
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)
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
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
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
What refers to untoward effects of drugs that are given in conventional therapeutic settings?
Adverse drug reactions
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
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
Menopausal hormone therapy (MHT) was formerly known as hormone replacement therapy HRT consists of what?
administration of estrogens with progestogen