Environmental and Nutritional Disorders Flashcards
Global Disease Burden (GDB)
estimates the burden imposed by environmental disease, 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 happened to the GDB from 1990-2010? Cause?
increase in mortality due to HIV/AIDS
What is the leading global cause of health loss?
undernutrition
What is the leading cause of death in developed countries?
ischemic heart disease and cerebral vasculature disease
What are 5 of 10 leading causes of death in developing countries?
Infectious disease
50% of all deaths in kids younger than 5 years are attributed to what 3 diseases?
pneumonia, diarrheal disease, and malaria
What are the categories of emerging infectious diseases?
newly evolved strains or organisms- multi-drug resistant TB
pathogens endemic to other species that recently “jumped” to human population-HIV
pathogens that have been present in human population, but increase in incidence- dengue fever due to warming
What will be the preeminent global cause of environmental disease if no action is taken?
climate change
What will the health impacts of climate change depend on?
extent and rapidity, nature and severity of the consequences, and our ability to mitigate the damage
Affects of heatwaves and air pollution in disease
Cardiovascular, cerebrovascular, and respiratory diseases worsten
Contamination from floods and disruption of clean water supplies causes
Gastroenteritis, cholera, and other food-borne and waterborne infectious diseases
Examples and causes of vector-borne infectious diseases
malaria, Dengue fever; increased temperature, crop failures, and more extreme weather variations
Disrupted crop production causes what?
malnutrition
Toxicology
distribution, effects, and mechanisms of action of toxic agents
How many pounds of toxic chemicals and unrecognized carcinogens are released per year in the US?
4 billion pounds; 72 million lbs carcinogens
Xenobiotics
exogenous chemicals in the environment (air, water, food, soil) that may be absorbed into the body (inhaled, ingested, skin contact)
Lipophilic
can transport and penetrate through the basement membrane; most solvents and drugs
Detoxification
when solvents, drugs, and xenobiotics are metabolized to an inactive water-soluble product
What is the other outcome for solvents, drugs, and xenobiotics besides detox?
activated to form toxic metabolites
Phase 1 reaction of xenobiotics
hydrolysis, reduction, oxidation
Phase 2 reaction of xenobiotics
glucoronidation, sulfation, methylation, and conjugation
Cytochrome P-450
located in ER of the liver, also present in skin, lungs, GI mucosa
catalyzes reactions that either detoxify xenobiotics or convert them into active compounds that cause cell injury
What byproduct can P-450 produce?
ROS–>cell damage
Is the CYP activity between people the same?
No, great variation
What decreases the action of CYP?
fasting and starvation
Who is more susceptible to air pollution?
persons with preexisting pulmonary or cardiac disease
What are the major causes of morbidity and mortality when it comes to pollution?
airborne microorganisms
What are there limits on regarding air pollution?
sulfur dioxide, carbon monoxide, ozone, nitrogen dioxide, lead, and particulate matter
Where is smog the highest?
Beijing, LA, Houston, Cairo, New Delhi, Mexico City, and Sau Paulo
Ground level ozone toxicity
mediated free radicals; injure respiratory tract epithelial cells and type I alveolar cells, releasing inflammatory mediators–>mild symptoms
Who is more affected by ozone toxicity?
people with asthma or emphysema
Sulfur dioxide toxicity
combines with ozone and particulate matter–>witches brew
How is sulfur dioxide toxic made?
power plants burning fossil fuels, copper smelting, and byproduct of paper mills
What symptoms does sulfuric acid and sulfuric trioxide cause?
burning sensation in nose and throat, difficulty breathing, and asthma attacks
Particulate matter (soot)
pulmonary inflammation and secondary CV effects
What are the most harmful particulate matters?
fine or ultrafine particles less than 10 micrometers in diameter
What happens to particulate matter over 10 micrometers?
removed in the nose or trapped by the mucociliary epithelium of the airway
Carbon monoxide
nonirritating, colorless, tasteless, odorless gas produced when there is incomplete oxidation of the hydrocarbons
Chronic carbon monoxide poisoning
working in tunnels, underground garages, and in highway toll booths with high exposure to car fumes
Acute carbon monoxide toxicity
in a small, closed garage, the average running car can produce sufficient CO to induce coma or death within 5 minutes
How does CO kill?
inducing CNS depression, widespread ischemic changes
basal ganglia and lenticular nuclei
If death occurs rapidly, NO morphological changes
Longer survival with CO poisoning- what does brain look like?
May be slightly edematous, with punctate hemorrhages and hypoxia-induced neuronal changes
Symptoms if pt survives CO poisoning
impaired memory, vision, hearing, and speech
Pathophysiology of CO poisoning
Hb has a 200-fold greater affinity for CO than O; systemic hypoxia–>20-30% saturated with CO
unconsciousness and death- 60-70% saturation in less than 5 minutes
Appearance of someone with CO poisoning
cherry red color of the skin and mucous membranes
Wood smoke
polycyclic hydrocarbons are carcinogens
Bioaerosols
Legionnaires disease, viral pneumonia, pet dander, fungi, molds
Radon
radioactive gas derived from uranium; increased lung cancer risk
Formaldehyde
building materials, poorly ventilated trailers following disasters; carcinogen
Sick building syndrome
indoor pollutants, poor ventilation; flood-hit buildings
damp homes–>molds like aspergillus and penicilium–>allergic rhinitis and recurrent sinitus
Symptoms of sick building syndrome
headache, chest infection, chest congestion, congestion of nose and around eyes
Why are fine or ultrafine particles more dangerous?
readily inhaled into the alveoli, releasing a number of inflammatory mediators
Lead
readily absorbed metal that binds to sulfhydryl groups in proteins and interferes with Ca2+ metabolism
What effects do lead lead to?
hematologic, skeletal, neurologic, gastrointestinal, and renal toxicities
How can you get lead poisoning?
flaking lead paint and soil- kids
occupational exposure
Where is most of the absorbed lead incorporated in the body?
bone and developing teeth, competes with calcium; stays in bones 20-30 years
Effects of low levels of lead
subtle deficits in intellect, behavioral problems, hyperactivity, poor organization skills in kids–>brain damage
Brain damage with lead poisoning
sensory, motor, intellectual, and psychological impairments; decreased IQ, learning disabilities, retarded psychomotor development, blindness
Brain damage with severe lead poisoning
psychoses, seizures, and coma
How does Pb toxicity in a mother affect a fetus?
impair brain development in prenatal infant
Adult peripheral neuropathies due to lead
CNS disturbances Wrist drop (extensors), followed by paralysis of the peroneal muscles (foot drop)
Lead lines
radiodense deposits in metaphyses (interferes with remodeling of cartilage); also lead lines in the gums
Lead and its affects on blood
heme deficit–>hypochromic microcytic anemia, basophilic stippling, and ring sideroblasts (iron-laden mitochondria)
Lead colic
extremely severe, poorly localized abdominal pain
Renal affects of lead
proximal tubule damage, chronic damage–>interstitial fibrosis and possible renal failure
Microcytic hypochromic anemia
MCV < 80 fL
MCH < 27 pg
due to lead poisoning
Ringed sideroblast
associated with sideroblastic anemia, due to excess iron in mitochondria
What size should RBCs be?
The neutrophil of a small lymphocyte
Mercury
binds to sulfhydryl groups, damage CNS and kidney
Main source of mercury
contaminated fish (methyl mercury), mercury vapors from metallic mercury in dental amalgams
Minamata disease
cerebral palsy, deafness, blindness, MR, and major CNS defects in children exposed to mercury in utero
Arsenic
interfere with cell metabolism–> toxicities most prominent in the GI tract, nervous system, skin and heart (Borgia and Medici poisonings)
Where can arsenic be found?
soil and water (natural); wood preservatives, herbicides, herbal medicines
Large quantities of arsenic ingested cause toxicity where?
GI, cardiovascular, and CNS
2-8 weeks postexposure of arsenic
sensorimotor neuropathy, paresthesias, numbness, pain
Chronic skin changes due to arsenic
hyperpigmentation and hyperkeratosis
Arsenic leads to increased risk for cancers where?
lungs, bladder, and skin (palms and soles)
Cadmium
toxic to kidney and lungs via uncertain mechanisms that may involve increased ROS
Source of cadmium
nickel-cadmium batteries, soil, plants= food
What diseases does cadmium cause?
obstructive lung disease, renal tubular damage, skeletal abnormalities associated with calcium loss
increased risk of lung cancer
Itai-Itai
ouch-ouch; Japan; osteoporosis and osteomalacia with renal disease
Toxicants that can cause lung cancer
radon, asbestos, silica, nickel, arsenic, chromium, mustard gas, uranium
Toxicants that can cause fibrosis
silica, asbestos, cobalt
Benzene causes what?
leukemia
Vinyl chloride causes what?
liver angiosarcoma
Examples of organic solvents that are occupational health risks
chloroform and carbon tetrachloride–>CNS depression and coma
Exposure to benzene and 1,3-butadiene causes increased risk of what? Who is affected?
leukemia; rubber workers
What does benzene and 1,3-butadiene do to the body?
marrow aplasia and increased risk of acute myeloid leukemia
Polycyclic hydrocarbons
from combustion of fossil fuels; scrotal cancers in chimney sweeps
most potent carcinogens–>lung and bladder cancer
Organochlorines
synthetic lipophilic products that resist degradation
What is an important organochlorine?
DDT used in pesticides
PCBs and dioxin are nonpesticide organochlorines
Dioxins and PCBs
folliculitis and dermatosis- chloracne
abnormalities in liver and CNS
Chloracne
due to dioxins and PCBs
acne, cyst formation, hyperpigmentation and hyperkeratosis, face and behind ears
Mineral dusts
coal dust, silica, asbestos, beryllium–>pneumonconioses
Asbestos
mineral dust–>mesothelioma, black dust
Ferruginous bodies
due to mineral dusts–> asbestos fibers coated in iron
appear blue
Vinyl chloride
angiosarcomas in liver
Bisphenol A (BPA)
line almost all food bottles and cans
potential endocrine disruptor
Tobacco
leading exogenous cause of human cancers, 90% of lung cancers
Is tobacco use dose dependent?
Yes, pack years
What happens with cessation of smoking tobacco?
within 5 years decreases overall mortality and risk of death from CV disease; lung cancer decreases 21% within 5 years, but the excess risk persists for 30 years
Nicotine
an alkaloid present in tobacco; not a direct cause of tobacco-related disease but is strongly addictive
What does nicotine do to the body?
Increases HR and BP
What does tobacco smoke affect and cause?
tracheobronchial mucosa–>inflammation and increased mucus production (bronchitis); emphysema
What are two potent carcinogens directly involved in the development of lung cancer?
polycyclic hydrocarbons and nitrosamines
Ten-fold higher incidence of lung carcinomas in what workers who also smoke?
asbestos workers and uranium miners
Multiplicative interaction
tobacco and alcohol–>laryngeal and oral cancers
What facilitates the excretion of carcinogens?
CYPs; some intermediates, though, are electrophilic and form DNA adducts that can cause mutations in oncogenes and tumor suppressors
What cancers are associated with cigarette smoke?
esophagus, pancreas, bladder, kidney, cervix, and bone marrow
What are the most common diseases caused by cigarette smoke involving the lung?
emphysema, chronic bronchitis, and COPD
What CV disease is smoking strongly linked to?
atherosclerosis–>MI
Multiplicative effect on MIs when combining smoking with what?
HTN and hypercholesterolemia
Maternal smoking increases the risk of what?
spontaneous abortions, preterm births, and intrauterine growth retardation (IUGR)
Passive smoke inhalation increases the risk of what?
1.3 x increased risk of lung cancer
risk of CAD and fatal MI
increased risk of asthma in children
The risk of lung cancer is determined by what?
the number of cigarettes smoked
Multiplicative increase in the risk of what kind of cancer from the interaction of alcohol and tobacco?
laryngeal cancer
Ethanol ingested is directly proportional to what?
blood level
amount exhaled proportional to blood level, also
What is the legal definition of drunk driving in the US?
80 mg/dL 0.8
How many drinks gets an average individual to the legal limit?
3 standard drinks
Level of alcohol that causes drowsiness?
200 mg/dL
Level of alcohol that causes stupor?
300 mg/dL
How is alcohol processed by the body?
oxidized to acetaldehyde in liver by alcohol dehydrogenase (ADH)–>acetate by ADH–>used by mito respiratory chain
Why does alcohol cause increased susceptibility to other compounds?
inhibits metabolism of other compounds
includes drugs, anesthetics, carcinogens, and industrial solvents
What does alcohol in high concentrations compete with? Causes?
CYP2E1 substrates
delays drug catabolism–>potentiates depressant effects of narcotic, sedative, and psychoactive drugs in the CNS
What molecule is required to convert acetylaldehyde to acetic acid in the mitochondria? Consequences?
NAD+
increased NADH associated with increased lactic acid levels and steatosis (due to low NAD)
Alcoholic cerebellar degeneration
atrophy of the superior part of the vermis
Acute alcoholism
mostly CNS effects (depressant), but also hepatic steatosis, acute gastritis, and ulceration
reversible if EtOH consumption discontinued
Chronic alcoholism
shortened lifespan due to damage to the liver, GI tract, CNS, CV system, and pancreas
Alcohol and the liver
main site of chronic injury; steatosis, alcoholic hepatitis, and cirrhosis
What is cirrhosis of the liver associated with in alcoholism?
portal hypertension and increased risk for hepatocellular carcinoma
GI and chronic alcoholism
bleeding from gastritis, gastric ulcer, and esophageal varices
Thiamine (vit B1) and chronic alcoholism
peripheral neuropathies and Wernicke-Korsakoff syndrome; cerebral atrophy, cerebellar degeneration, and optic neuropathy
Alcoholic cardiomyopathy
dilated congestive cardiomyopathy, HTN; decreased HDL–>increased risk of CAD
Alcoholism and the pancreas
acute and chronic pancreatitis
Fetal alcohol syndrome
microcephaly, growth retardation, and facial anomalies in newborn; decreased mental function as child grows; first trimester most harfmul
Malnutrition and nutritional deficits and alcoholism
Vitamin B especially
Minocycline can cause what to the skin?
discoloration; adverse drug reaction
Drug-induced hypersensitivity reactions most commonly present as what?
skin rashes
Anticoagulant
warfarin (vitamin K antagonist) and dabigatran (inhibits thrombin)
causes bleeding; thrombosis due to insufficient dosage (stroke)
Menopausal hormone therapy (MHT)
estrogens with progesterone; not good long term
Oral contraceptives
do NOT increase breast cancer risk; increase cervical cancer due to HPV; increased risk of venous thrombosis and PE; does NOT increase CAD in women under 30, but increases it 2x in smokers
hepatic adenoma- rare and benign, older pt with prolonged OC use
Anabolic steroids
stunted growth, acne, gynecomastia, testicular atrophy; facial hair and menstrual changes in females; psychiatric issues; increased risk MI
Acetaminophen
50% unintentional OD; 50% of acute liver failures with 30% mortality; centrilobular necrosis
Aspirin
acute salicylate poisoning affects the brain–>nausea–>coma
chronic (salicylism)–>HA, dizziness, tinnitus, bleeding, coma; analgesic nephropathy
How is acetaminophen metabolized 95% of the time?
detox by phase II enzymes–>excretion in urine as glucuronate or sulfate conjugate–>no toxicity
How is acetaminophen metabolized 5% of the time?
CYP2E1 activity–>NAPQ–>protein adducts lipid peroxidation–>hepatocyte necrosis–>liver failure
Opiates cause what?
profound respiratory depression, arrhythmia, cardiac arrest, and pulmonary edema
10% of the time, what infection occurs with opiates?
endocarditis right heart valves
Methamphetamine causes what?
violent behavior, confusion, psychotic symptoms
Marijuana
increases HR, can increase or decrease BP which may cause right angina in pt with CAD; cognitive and psychomotor impairment with continued use; large numbers of carcinogens in smoke
Huffing/glue sniffing
MRI-detectable brain damage that ranges from mild-severe dementia
Cocaine
tachycardia, HTN, and peripheral vasoconstriction
coronary artery vasoconstriction and platelet aggregation–>thrombus–myocardial ischemia
lethal arrhythmias (NOT dose dependent)
decreased blood flow to placenta–>fetal hypoxia and spontaneous abortion
hyperpyrexia and seizures
Clinical significance of burn injury depends on what?
depth of burn, % of body surface covered by burn
internal injuries: inhalation of toxic fumes and heat
Treatment of burns
fluid and electrolyte management and infection control
1st degree burn
superficial; epidermis only
2nd degree burn
partial thickness; epidermis and dermis
3rd degree burn
full thickness; extend into the subcutaneous tissue
Shock in regards to thermal injuries
burns greater than 20% of body surface–>rapid shift of body fluids into interstitial compartment–>shock
Clinical signs of shock due to thermal injuries
generalized edema, pulmonary edema, can be severe
hypermetabolic state
Sepsis due to burns
all burns are colonized; Pseudomonas aeruginosa, MRSA, Candida
Respiratory insufficiency due to burns
24-48 hrs, direct heat effects on upper airway and inhalation of noxious gases
Pugilistic stance
looks like a boxer; burned beyond recognition
Hyperthermia
heat stroke= lack of sweating
Malignant hyperthermia
“heat stroke-like”; rise in core body temperature and muscle contractures in response to common anesthetics; RYR1 gene
Hypothermia
body temp < 90 degrees–> loss of consciousness, bradycardia, then Afib
2 types of electrical injury
burns and lightening classic high-voltage electrical injury
ventricular fibrillation or cardiac-respiratory failure
Radiation units
Curie (CI), gray (Gy), Sievert (Sv)
Curie
radiation emitted
Gray
energy absorbed
Sievert
the equivalent dose corresponds to the absorbed dose (grays) multiplied by the relative biological effectiveness of the radiation
Determinants of effect of ionizing radiation on DNA
rate of delivery field size cell proliferation O2 effects and hypoxia vascular damage
Indirect effect of ionizing radiation
ionization–>free radical formation–>DNA damage
Morphology of ionizing radiation
nuclear swelling, giant cells, pleomorphic nuclei, > 1 nucleus, cytoplasmic swelling
What happens to irradiated vessels in ionizing radiation?
endothelial cell proliferation, collagenous hyalinization and thickening of the intima–>marked narrowing or even obliteration of the vascular lumens
What causes scarring and contractions caused from ionizing radiation?
increased interstitial collagen in the irradiated field
What cells histologically look like cancer cells and why?
radiation-injured cells; cellular pleomorphism, giant-cell formation, conformational changes in nuclei, and abnormal mitotic figures
Cancer risks from radiation exposure
increased incidence of leukemias and solid tumors in Hiroshima and Nagasaki survivors
thyroid cancers in survivors of Chernobyl
increased frequency of leukemias and birth defects in Marshall islands
development of secondary cancers such as acute myeloid leukemia, myelodysplastic syndrome, and solid tumors in individuals who received radiation therapy for cancers such as Hodgkin’s lymphoma
Subintimal fibrosis
radiation-induced chronic vascular injury; occludes the lumen
Malnutrition
protein energy malnutrition, PEM; consequence of inadequate intake of proteins and calories or deficiencies in the digestion or absorption of proteins–>loss of fat and muscle tissue, weight loss, lethargy, and generalized weakness
Obesity leads to
diabetes, atherosclerosis, and cancer
Primary dietary insufficiency
missing from diet
Secondary dietary insufficiency
malabsorption, impaired utilization or storage, excess loss or increased need
What causes dietary insufficiency?
poverty, infections, acute and chronic illnesses, chronic alcoholism, ignorance, self-imposed dietary restrictions, GI diseases, and malabsorption syndrome
Protein-energy malnutrition (PEM)
50% deaths in infancy and childhood in developing countries; older and debilitated patients in nursing homes and hospitals
Weight loss of more than how much is associated with PEM in nursing home patients?
5%; increased mortality in nursing home pts
Signs of secondary PEM
depletion of subcutaneous fat in the arms, chest wall, shoulders, or metacarpal regions, wasting of the quads and deltoid muscles, and ankle or sacral edema
Marasmus
weight <60% normal for sex, height, and age; growth retardation and muscle loss
serum albumin normal; anemia; immune deficiency
Muscle proteins and sub! fat used as fuel–>emaciated extremities
Kwashiorkor
decreased protein more severe–>decrease in total calories
Hypoalbuminemia is seen with what malnutrition disease?
Kwashiorkor
generalized or dependent edema–>vitamin deficiency, immune deficiency and secondary infections
Other symptoms of Kwashiorkor
depletion of visceral protein compartment; fatty liver; sparing of subQ fat and muscle
chronic diarrhea, protein loss enteropathies, nephrotic syndrome, extensive burns, fat diets or replacement of milk with rice-based beverages
Cause of Kwashiorkor in Ghana and Southeast Asia
weaned too early and fed carb diet
Cachexia
PEM complication in AIDS or advanced cancers
50% of cancer pts; GI, pancreatic, and lung cancers
extreme weight loss, fatigue, muscle atrophy, anemia, anorexia, and edema
mortality from atrophy of the diaphragm and other respiratory muscles
Mechanism of cancer cachexia
NF kappa B is activated–>muscle specific ubiquitin ligases–>ubiquitinylation of myosin heavy chains–>proteasome–>loss of myofibrils, loss of muscle mass
Anorexia nervosa
self-induced starvation–>market weight loss
highest death rate of any psychiatric DO
amenorrhea, decreased thyroid hormone, decreased bone density
Bulimia
binge/purge; more common than anorexia and better prognosis
Electrolyte imbalance (hypokalemia)–>cardiac arrhythima
pulmonary aspiration of gastric contents
esophageal and gastric rupture
What is a complication of both anorexia and bulimia?
cardiac arrhythmia and sudden death due to hypokalemia
Vitamin A
retinol, retinal, and retinoic acid
Purpose of Vitamin A
maintenance of normal vision, regulation of cell growth and differentiation and regulation of lipid metabolism
Secondary Vitamin A deficiency can be seen with what other disorders?
Fat malabsorption (celiac disease, Crohn disease, colitis, CF, bariatric surgery, mineral oil laxative)
When do Vitamin A deficiencies in kids occur?
stores depleted when they have infections; absorptio of vitamin A poor in newborns
Effects of Vit A deficiencies
Night blindness
Epithelial/squamous metaplasia and keratinization
Xeropthalmia (dry eyes), Bitot spots, keratomalacia
Squamous metaplasia of the respiratory epithelium
Vitamin A deficiency result; increase in pulmonary infections
Immune deficiency in Vitamin A deficiency
increased mortality rates from common infections
Actue Vit A toxicity
headache, dizziness, V, stupor and blurred vision; confused with pseudotumor cerebri
Chronic Vit A toxicity
weight loss, anorexia, N&V, bone and joint pain
Vitamin D
Cholecalfciferol, Vitamin D3
Fat-soluble Vitamin D purpose
maintenance of adequate plasma levels of calcium and phosphorous to support metabolic functions, bone mineralization, and neuromuscular transmission
What is Vit D required to prevent?
rickets, osteomalacia, and hypocalcemic tetany
Rickets
frontal bossing, squared head, rachitic rosary, pigeon breast deformity, lumbar lordosis, bowing of the legs
Osteomalacia
inadequate mineralization of bone, weak and prone to fracture
Immune response of Vit D
helps clear Mycobacterium tuberculosis infections
Vitamin D metabolism
endogenous synthesis from 7-dehydrocholesterol, in a photochemical reaction that requires solar or artificial UV light
Insufficient sunlight and Vit D deficiency
decreased serum Ca and P–>Increased PTH–> mobilization of Ca and P from bones–>decreased serum Ca and P product–>poor bone mineralization
What is lost in rickets?
cartilage palisades
Vitamin C
ascorbic acid
Deficiency of water-soluble Vit C
scurvy, bone diseases in growing children, hemorrhages, and healing defects in children and adults
Where do we get Vit C?
Not synthesized endogenously; strictly from diet
Milk, liver, fish, abundant in fruits and vegetables
Secondary Vit C deficiency
older individuals that live alone and chronic alcoholics, have erratic and inadequate eating patterns
Vitamin C deficiency
poor vessel support results in bleeding tendency, inadequate synthesis of osteoid, impaired wound healing
Acrodermatitis enteropathica
rash around eyes, mouth, nose, and anus due to zinc deficiency
Iron deficiency causes what
hypochromic microcytic anemia
Iodine deficiency causes what
goiter and hypothyroidism
Copper deficiency causes what?
muscle weakness, neuro defects, abnormal collagen cross-linking
Fluoride deficiency causes what
dental caries
Selenium deficiencies cause what
myopathy, cardiomyopathy (Keshan disease)
Obesity is associated with what?
excess adiposity (obesity) and excess body weight associated with increased incidence of type 2 DM, dyslipidemias, CV disease, HTN, and cancer
Obesity
an accumulation of adipose tissue that is of sufficient magnitude to impair health
Normal BMI of obese pt
Greater than 30 kg/m2
Normal BMI
18.5-25
Overweight BMI
between 25 and 30
Central, or visceral, obesity
fat accumulates in trunk and abdominal cavity (mesentery and around viscera); associated with increased risk for several diseases–>excess accumulation of fat diffusely in subcutaneous tissue
Regulation of energy balance
involves Hypothalamus, leptin, insulin, ghrelin, intestines, and food intake, energy expenditure, and energy balance
Leptin
increases POMC/CART–>catabolic–>MC3/4R, alpha MSH–>causes endocrine and autonomic to secrete TRH and CRH–>energy consumption
also inhibits NPY/AgRP
Pyy (intestines)
inhibits NPY/AgRP
Ghrelin (stomach)
activates NPY/AgRP–>anabolic–> NPY and Y1/5 receptors–>behavioral releases MCH, orexins–>food intake
Metabolic syndrome
visceral or intra-abdominal adiposity, insulin resistance, hyperinsulinemia, glucose intolerance, HTN, hypertriglyceridemia, and decreased HDL
obesity is the main driver
Hypertriglyceridemia and low HLD is seen in what pts? Risks?
Obese people; CAD
What affect on the liver does obesity have?
nonalcoholic fatty liver disease
What is 6x greater in obese pts than lean ones?
Cholelithiasis (gallstones)
Pickwickian syndrome
hypoventilation syndrome associated with obesity
Hypersomnolence–>sleep apnea, polycythemia, and eventual right sided heart failure (cor pulmonale)
Marked adiposity predisposes to the development of what?
osteoarthritis
What kind of cancers are at increased risk in obese patients?
esophagus, pancreas, colon, rectum, breast, endometrium, kidney, thyroid, and gallbladder
What does insulin resistance lead to?
hyperinsulinemia–>increased free insulin like growth factor-1; mitogen
What does obesity increase the synthesis of?
estrogen
What can the proinflammatory state that is associated with obesity be?
carcinogenic
Aflatoxin
hepatocellular carcinoma
Nitrosamines and nitrosamides
gastric carcinomas
High animal fat and low fiber
colon cancer
Total dietary fat positively correlates with what?
breast cancer
Vit C and E, beta-carotenes, and selenium seem to have what affects due to antioxidant properties?
Anticarcinogenic
What kind of cancer does arsenic poisoning lead to?
Angiosarcoma of the liver
What microbe is associated with burns and necrosis caused by burns?
Pseudomonas aeruginosa
