Environmental and Nutritional Disorders Flashcards
Global disease burden (GDB)
Estimates the burden imposed by environmental diseases, including those caused by communicable and nutritional diseases.
Disability adjusted life year (DALY)
Sum of years of life lost due to premature mortality and disability in a population.
What are some major diseases that affected GDB from 1990-2010? (5)
HIV/AIDS Undernutrition Ischemic heart disease and cerebral vascular disease Infectious disease Post-natal diseases
Categories of emerging infectious diseases:
- Newly evolved strains/organisms
- Pathogens endemic to other organisms that now affect humans
- Pathogens that have previously been present in humans, but show an increase in incidence
- Newly evolved strains/organisms: multidrug resistant TB
- Pathogens endemic to other organisms that now affect humans: HIV
- Pathogens that have previously been present in humans, but show an increase in incidence: dengue fever, due to warming and spread into southern US.
Which diseases/conditions have been negatively impacted by climate change?
CV disease, cerebrovascular disease, respiratory diseases - worsened by heatwaves and air pollution.
Gastroenteritis, cholera, foodborne and waterborne infectious diseases - contamination from floods and changes in clean water supply.
Vector-borne diseases - malaria, dengue fever - due to increased temp., crop failures, and extreme weather variations.
Malnutrition - disrupted crop production.
Most solvents and drugs are:
How is that clinically important?
Lipophilic.
They can cross membranes.
What are the 3 phase I reactions?
Hydrolysis
Reduction
Oxidation
What are the 4 phase II reactions?
Glucoronidation
Sulfation
Methylation
Conjugation
Where are cytochrome p450s located?
ER of liver, but also skin, lungs, GI mucosa and others.
Cytochrome p450 reactions can either:
Detoxify xenobiotics orless commonly convert them into active compounds that cause cell injury
What is the effect of fasting and starvation on CYP activity?
Decreases CYP activity
Air pollution is especially hazardous to which patients? (2)
Patients w/ pre-existing pulmonary or cardiac diseases.
What does the EPA limit in outdoor air pollution? (6)
SO2 CO O3 NO2 Lead Particulate matter
Effects of ozone on:
Healthy adults and children: (3)
Athletes, outdoor workers, asthmatics: (2)
Healthy adults and children: decreased lung function, increased airway reactivity, lung inflammation.
Athletes, outdoor workers, asthmatics: decreased exercise capacity, increased hospitalizations.
Effects of SO2 on:
Healthy adults: (1)
People with chronic lung disease: (1)
Asthmatics: (2)
Healthy adults: respiratory symptoms.
People with chronic lung disease: increased mortality.
Asthmatics: increased hospitalizations, decreased lung function.
Ozone toxicity is due to:
What do they damage?
Free radicals.
Respiratory tract epithelial cells and type I alveolar cells and release inflammatory mediators.
What is “witches’ brew”?
What produces it?
What symptoms ensue?
SO2 + O3 + particulate matter.
Power plants burning fossil fuels, copper smelting and byproduct of papermills.
Burning sensations in nose and throat, trouble breathing and asthma attacks.
Particulate matter (soot) has what effects? (2)
What size particulate is most harmful?
Pulm inflammation, secondary CV effects.
Fine or ultrafine particles less than 10 um in diameter.
CO toxicity can occur in which 2 scenarios?
Chronically working in tunnels, garages, highway toll booths with lots of exposure to car fumes.
Acutely by being trapped in a garage within approx 5 min.
What does CO do physiologically?
What are its effects with longer survival?
What are the symptoms if the patient recovers?
What is a hallmark sign of CO poisoning?
Inducing CNS depression leading to ischemic changes to basal ganglia and lenticular nuclei. Also, outcompetes Hb for O2
Longer survival in the brain may be slightly edematous w/ punctate hemorrhages and hypoxia-induced neuronal changes.
Memory, vision, hearing and speech problems.
Generalized cherry-red color of skin and mucous membranes.
Systemic hypoxia shows how much saturation of Hb with CO?
How much saturation is associated with death and unconsciousness?
20-30%.
60-70%
Wood smoke produces ______ which are carcinogenic.
Polycyclic hydrocarbons
Bioaerosols examples: (3)
Diseases caused by bioaerosols? (2)
Pet dander, fungi, mold.
Legionnaires disease, viral pneumonia.
Formaldehyde is a carcinogen. Where does it come from? (2)
Building materials
Poorly ventilated trailers following disasters
What causes sick building syndrome?
Indoor pollutants, poor ventilation.
Lead as a pollutant
It is readily absorbed and binds to sulfhydryl groups in proteins that interfere with Ca++ metabolism, effects that lead to hematologic, skeletal, neurological, GI and renal toxicities.
Where can lead be found?
Paint
Soil
Occupational exposure: batteries, pigments, radiators and tin cans.
Where does most of the absorbed lead get incorporated?
Bone and developing teeth
Low level Pb can have what effects in kids?
Intellectual, behavioral, hyperactivity and poor organizational skills in kids.
What does Pb do the baby while mom’s pregnant?
Impairs brain development.
CNS disturbances from lead poisoning in adults include:
Peripheral neuropathies leading to wrist drop, followed by foot drop.
What are lead lines?
Radiodense deposits on metaphyses which interfere with cartilage remodeling.
Lead “colic”
Severe, poorly organized abdominal pain
What effects can Pb have on the kidneys?
Proximal tubule damage; chronic damage -> interstitial fibrosis and possible renal failure.
Ringed sideroblast
Associated w/ siderblastic anemia, due to excess iron in mitochondria.
Mercury’s toxicity
Main 2 sources:
What is Minamata disease?
Binds sulfhydryl groups and damages CNA (developing brain) and kidneys.
Contaminated fish, mercury vapors from dental amalgams.
Includes cerebral palsy, deafness, blindness, MR and major CNS defects in children exposed in utero.
Arsenic toxicity
Where is it found?
Interferes with cellular metabolism -> toxicities most common in GI tract, nervous system, skin and heart (Borgia and Medici poisonings).
Soil and water naturally. Wood preservatives, herbacides, herbal meds.
What happens when large quantities of arsenic are ingested?
2-8 wks post exposure?
GI, CV and CNS toxicities.
Sensorimotor neuropathy; paresthesias, numbness, pain.
What chronic skin changes occur in arsenic poisoning?
Hyperpigmentation and hyperkeratosis
Which cancers are at a higher risk for people with arsenic poisoning?
Lung, bladder and skin (palms and soles)
Cadmium toxicity
Where is it found?
What diseases can ensue?
Increased risk for?
Preferentially toxic to kidneys and lungs via uncertain mechanisms that may increase ROS.
Nickel-cadmium batteries, soil, plants = food.
Obstructive lung disease, renal tubular damage, skeletal abnormalities from Ca++ loss.
Increased risk for lung cancer.
Chloroform and carbon tetrachloride can lead to:
Dizziness and confusion -> CNS depression and coma.
Lower levels toxic to liver and kidneys.
What molecules, when rubber workers are exposed, can increase risk of leukemia?
How can this lead to acute myeloid leukemia? (AML)
Benzene and 1,3-butadiene
Dose-dependent marrow aplasia
Polycyclic hydrocarbons can cause which cancers? (3)
Scrotal cancer, lung and bladder cancers
What are some examples of organochlorides?
What is their toxicity?
DDT, PBs, dioxin.
Disrupt hormonal balance due to antiestrogenic or antiandrogenic activity.
Effects of Dioxins and PCBs
Chloracne (acne, cysts, hyperpigmentation and hyperkeratosis of face and ears).
Abnormalities in liver and CNS.
Mineral dusts cause:
Pneumonconioses
What are ferruginous bodies?
Asbestos fibers coated in iron
Vinyl chloride can cause:
Angiosarcomas in the liver
BPA (bisphenol A) has what effects?
Where is it found?
Endocrine disruption.
Lines almost all food bottles and cans
Nicotene does what?
Binds nAChRs in the brain and releases catecholamines from SNS neurons -> increased HR, BP and CO.
Agents in smoke lead to: (2)
Inflammation and increased mucous production
How does emphysema occur in smoking?
WBC recruitment which increases local elastase production and injury to lung tissue.
Which cancers is smoking associated with?
Lung Esophagus Pancreas Bladdr Kidney Cervix Bone marrow
How is the amount of alcohol absorbed in the stomach and SI related to blood level?
Directly proportional
Legal limit of alcohol in blood
Drowsiness
Stupor
Coma
80mg/dl (after 3 drinks)
200mg/dl
300mg/dl
> 300mg/dl
What is EtOH metabolized to? By what?
Who utilizes it?
What does it compete with?
What does it potentiate?
Acetaldehyde by ADH.
Mitochondrial respiratory chian.
CYP2E1 to potentiate depressant effects of narcotic, sedative and psychoactive drugs in the CNS.
Atrophy of the superior part of the vermis is known as:
Alcoholic cerebellar degeneration
Acute alcoholism effects:
Chronic alcohol effects:
CNS depressant, but also hepatic steatosis, acite gastritis and ulceration.
Shortened lifespan of liver, GI tract, CNS, CVS and pancreas.
Thiamine deficiency from alcoholism leads to:
Peripheral neuropathies and Kernicke-Worsakoff syndrome; cerebral atrophy, cerebellar degeneration and optic neuropathy.
Alcoholic cardiomyopathy
Dilated congestive cardiomyopathy, HTN.
Leads to low HDL which increases risk of CAD.
Fetal alcohol syndrome sx
Microcephaly, growth retardation, facial anomalies.
What are some positives of drinking moderate amounts of alcohol? (3)
Increased HDL
Inhibit platelet aggregation
Low fibrinogen levels may protect against CHD
Anticoagulants s/e (2)
Bleeding; thrombosis due to insufficient dosage.
Oral contraceptives s/e
Increased risk for cervical cancer
Increased risk for VT
Hepatic adenoma
Anabolic steroids s/e
Stunted growth, acne, gynecomastia, testicular atrophy; facial hair & menstrual changes in females; psychiatric issues; ↑risk MI
Acetaminophen s/e (2)
Acute liver failure
Centrilobular necrosis
Aspirin s/e
Acute salicylate poisoning effects the brain →nausea →coma; chronic (salicylism) HA, dizziness, tinnitus, bleeding, coma; analgesic nephropathy
Opiates s/e
Profound respiratory depression, arrhythmia, cardiac arrest, and pulmonary edema
Methamphetamine s/e
Violent behavior, confusion, psychotic sx
Huffing/glue sniffing s/e
MRI-detectable brain damage ranging from mild to severe dementia
Bath salts s/e
Agitation, psychosis, MI, & suicide
Cocaine s/e
Tachycardia, HTN, peripheral vasoconstriction.
1st
2nd
3rd
Degree burns
1st: superficial, epidermis only.
2nd: partial thickness; epidermis and dermis.
3rd: full thickness; extends into subcutaneous tissues.
How does shock ensue from a burn?
When approx >20% of body surface is burnt -> rapid shift of fluid into interstitium -> shock
How does a burn lead to sepsis?
Virtually all burns can be colonized by pseudomonas aeruginoa, MRSA and candida.
4 outcomes of severe burns
Shock
Sepsis
Respiratory insufficiency
Hypertrophic scars
Malignant hyperthermia
What gene is associated?
“Heat stroke like” rise in core body temp and muscle contractures in response to anesthetics. Associated with RYR1 gene.
Sx of hypothermia (3)
Body temp <90 -> loss of consciousness, bradycardia and AFib.
Morphology of cells exposed to radiation
What are the cancer risks for these cells?
Similar to cancer cells.
Nuclear swelling, giants cells, many nuclei, etc.
Leukemias and solid tumors of the thyroid, breast and lungs.
What is subintimal fibrosis?
It is fibrosis that occludes the lumen from radiation injury
Primary vs secondary malnutrition
Primary is missing from diet.
Secondary is malabsorption, storage disease, etc.
Protein-energy malnutrition (PEM) is a major cause of death for which patients?
Infants/children and elderly people in nursing homes.
Signs of PEM (3)
(1) depletion of subcutaneous fat in the arms, chest wall, shoulders, or metacarpal regions; (2) wasting of the quadriceps and deltoid muscles; (3) ankle or sacral edema
Marasmus
wt <60% NL for sex, ht and age; growth retardation and muscle loss.
Serum albumin NL; anemia; immune deficiency.
Muscle proteins & subQ fat used as fuel → emaciated extremities
Kwashiorkor
↓protein more severe > ↓ in total calories
Hypoalbuminemia→ generalized or dependent edema; vit def, immune def & secondary infections
Depletion of visceral protein compartment; fatty liver; sparing of subQ fat and muscle
Weaned too early, and fed carbohydrate diet (Ghana & Southeast Asia)
Chronic diarrhea, protein losing enteropathies, nephrotic syndrome, extensive burns, fad diets or replacement of milk with rice-based beverages
Cachexia
PEM complication in AIDS or advanced cancers
•50% of cancer pts; GI, pancreatic and lung cancers
•Extreme wt loss, fatigue, muscle atrophy, anemia, anorexia, and edema
•Mortality from atrophy of the diaphragm and other respiratory muscles
What is the mechanism for cachexia?
Tumor and host secrete TNF and PIF which activate NF-kB which activate transcription of ubiquitin ligases which breaks down muscle proteins (myosin).
Anorexia nervose
Self-induced starvation →mkd wt loss
•Highest death rate of any psychiatric DO
•Amenorrhea, ↓thyroid hormone, ↓ bone density
Bulimia
Binge/purge; more common than anorexia and better prognosis
•Electrolyte imbalance (hypokalemia) → cardiac arrhythmia
•Pulmonary aspiration of gastric contents
•Esophageal and gastric rupture
What are the 2 major risks for anorexia nervosa and bulimia?
Susceptibility to cardiac arrhythmia and sudden death due to hypokalemia
Radon increases risk for:
Increased risk for lung cancer
Pb leads to a heme deficiency. What does this cause? (3)
Hypochromic microcytic anemia, basophilic stipping and ring sideroblasts
What is Itai-Itai?
Osteoporosis and osteomalacia with renal disease from cadmium poisoning.
Defects associated with Vit A deficiency (4)
Night blindness
Epithelial/squamous metaplasia and keratinization
Bitot spots in the eyes
Immune deficiency
Acute Vit A toxicity
Chronic Vit A toxicity
Acute - headache, dizziness, stupor, blurred vision; confused w/ pseudotumor cerebri.
Chronic - wt loss, anorexia, bone and joint pain.
What is secondary Vit A deficiency associated with?
What diseases cause it?
Fat malabsorption.
Celiac dz, Crohns dz, CF, bariatric surgery.
Normal BMI range
Overweight range
18.5 to 25 kg/m2
25 kg/m2 to 30 kg/m2
Consequences of obesity
Metabolic syndrome Hypertriglyceridemia and low HDL Nonalcoholic fatty liver dz Hypoventilation syndrome Sleep apnea Cor pulmonale (right heart failure) Osteoarthritis
Aflatoxin ->
Nitrosamines and nitrosamides ->
High animal fat and low fiber ->
High total dietary fat ->
Aflatoxin -> hepatocellular carcinoma
Nitrosamines and nitrosamides -> gastric carcinomas
High animal fat and low fiber -> colon cancer
High total dietary fat -> breast cancer
Anticarcinogens (4)
Vit C
Vit E
beta-carotenes
Selenium
