Chapter9 Flashcards
what is the DALY
disabilty adjusted life year, metric that combines yrs lotted to premature mortality and yeras lived with illness and disability
what is the leading global cause of health loss in developing countries vs developed
developing is undernutrition
coronary/CV in developed
5/10 top causes of death
infection related
what are xenobiotics
exogenous environmental agents inhaled, ingested and absorbed
what type of compounds readily cross plasma membranes
lipophilic compounds with increased blood transport due to lipoproteins
What are the 2 groups of drug-metabolizing enzymes
phase I: enzyme include hydrolysis, oxidation and reduction
phase II: enzymes include glucuronidation, sulfation, methylation, conjugation
What are the main phase I drug metabolizing enzymes
cytochrom P450 (CYP) enzymatic activity releases ROS
What organ is most affected by outdoor air pollution
lungs. dec pulmonary function, increased airway reactivity and infections. dec mucociliary clearance
What are the major components of smog at lower atmosphere
contains NOs and colatile organic compounds
What is the main source of sulfur dioxide in atmosphere
coal and oil combustion
copper smelting
paper manufacturing
what are the clinical results of sulfur dioxide pollution
dyspnea, airway hyperreactivity
how come smaller particulate matter is more deleterious to the lungs
because the >10 microns are trapped in nasal mucus/upper respiratory tract
What does CO cause
impaired resp function
acute poisoning: CNS depression and systemic hypoxia and characteristic cherry-red coloring from increased carboxyhemoglobin
What type of toxins are in wood smoke
carcinogenic polycyclic hydrocarbon
What is radon
radioactive gas from uranium decay in soil that increases risk in cancer
what does fromaldehyde toxicity cause
acute aye and upper respiratory irritation
Why are children at higher risk for lead poisoning
increased GI absorption and increased permeable blood-brain barrier
What are the neurological risks of lead poisoning and why
competes for Ca ion
in children causes psychomotor impairments
in adults causes peripheral demyelinating neuropathy
what are the hemolytic risks of lead poisoning
decrease in heme-synthesis enzymes and iron incorporation
leading to microcytic, hypo chromic anemia
how does lead poisoning affect bone growth
changes the bone healing at epiphyses decreasing bone healing
what is lead colic
abdominal pain and anorexia
Why is the brain susceptible to mercury
lipid soluble, CNS accumulations with increased binding affinity for cellular thiol groups
what form of arsenic is most toxic
ArO3
ingestion of arsenic can cause what
GI, CV and neurosequalae via dec mitochondrial ox-phos
What occurs with ingestion of Cadmium
skeltal changes due to Ca loss
how does cadmium poisoning lead to obstructive lung disease and renal tubular damage
alveolar Macrophage necrosis
Why does cadmium cause an increase in lung cancer
from dNA damage induced by ROS
What does chloroform toxicity cause
acute CNS depression, liver and kidney toxicity
aromatic hydrocarbons like benzene are metabolized how and cause what
CYP2E1 and the toxic metabolites disrupt marrow hematopoiesis with increased risk of AML
what is released from fossil fuel combustion and what does it cause
polycyclic hydrocarbons
increased risk of lung and bladder CA
What are pesticides like DDT and non-pesticides like PCB and dioxin? What do they cause
organochlorines
DDT causes endocrine disruption with anti-estrogenic/androgenic effects
Dioxin and PCB cause folliculitis, dermatosis, hepatic and CNS alterations activating CYP
What can hapen from toxic mineral dust inhalation
chronic, non-neoplastic diffusely fibrosing pneumoconiosis
What occurs with vinyl chloride toxication
angiosarcoma of liver
what can occur with phthalate toxication
endocrine disruption, testicular dysgenesis syndrome
What is the mechanism of nicotine and what does it cause
binds CNS R releasing catecholamines that increase HR< BP and cardiac contractility
What causing Cancer from smoking
carcinogenic polycylic hydrocarbons, benzopyrene, nitosamines in smoke
CYP modification increases carcinogenicity in lung, oral cavity, esophagus, pancreas, bladder, laryngeal CA
what are other Dx from smoking
tracheobronchial inflammation
bronchitis
emphysema from elastase production
atherosclerosis, MI from platelet aggreagation, endothelial dysfunction, myocardial hypoxia
What can maternal- smoking cause
fetal hypoxia with decreased intrauterine growth and increased spontaneous abortion, increased change preterm birth
at what level of alcohol causes drowsiness? stupor?
drowsy at 200 mg/dL
stupor at 300
coma at levels above
How do chronic alcoholics have increased tolerance to alcohol
hepatic CYP induction
how is EtOH metabolized
acetaldehyde via cytosolic ADH
What does hepatic acetaldehyde dehydrogenase do
convert acetaldehyde to acetate used by mitochondria
What CYP does alcohol require for metabolism
CYP2E1
What occurs in people with an inactive copy of the ALDH enzyme
1/2 asians, they cannot oxidize acetaldehyde
nausea, flushing, tachycardia, hyperventilation
why does the liver accumulate fat from alcohol
ADH oxidation of EtOH reduces NAD to NADH and NAD is required for fatty acid oxidation and lactic acid to pyruvate
What happens with EtOH in the GI tract
endotoxin release from gut flora with inflammatory cytokine production
What are signs of acute alcohol injury
heaptic steatosis, gastritis and ulceration, CNS depression
What are the liver changes in chronic alcoholism
fatty change, alcoholic hepatitis, cirrhosis assoc
portal HTN and risk for hepatocellular carcinoma
What are the GI changes in chronic alcoholism
massive bleeding due to acute gastritis and ulceration or esophageal varices from portal HTN
How does chronic alcoholism affect the brain
thiamine deficiency from poor nutrition can lead to peripheral neuropathy, Wernicke-Korsakoff syndrome, cerebral atrophy, cerebellar degeneration, optic neuropathy
what are the heart effects from chronic alcoholism
dilated cardiomyopathy assoc with increased HTN incidence, inc EtOH, dec liver HDL
what are the pancreatic effects from chronic alcoholism
increase risk of acute and chronic pancreatitis
How does chronic alcoholism affect fetal growth
developmental defects, consumption during first trimester is most harmful
What type of CA are associated with chronic alcoholism
oral cavity, pharynx, esophagus, liver, possibly breast due to acetaldehyde metabolite
What are sirtuins
histone deacetylases
What is the catch 22 of Hormone replacement therapy
alleviates menopausal Sx, dec osteoporosis
increased risk of breast CA and thromboembolism
What are the risks of oral contraceptives
3x inc risk venous thrombosis and pulmonary thromboembolism from increased hepatic synthesis of coagulation factors
increase risk MI in smokers
inc ovarian and endometrial CA
hepatic adenoma
what is a risk factor for someone that owudl prevent them from taking oral contraceptives
factor V or prothrombin mutation carriers
How does synthetic testosterone lead to testicular atrophy and gynecomastia in men, virilizaiton in women
increase dose feedback so decreased LH and FSH production
What drug is responsible for 50% acute liver failure in US
acetominophen
What metabolizes acetaminophen
phase II hepatic enzymes mainly
then CYP2E—> NAPQ1 conjugated with glutathione
how does increased acetaminophen affect liver
glutathione depletion, ROS injury, inc NAPQ1 complexes with hepatocyte membrane proteins and mitochondria causing degradation
what are th symptoms of aspirin overdose
respiratory alkylosis–>metabolic acidosis
what are the symptoms of chronic aspirin toxicity
HA, dizzyness, tinnitus, mental confusion, drowsiness, nausea, vomiting, diarrhea
what can cause renal papillary necrosis
long-term ingestion of aspirin and phenacetin mix
What are the sideeffects of cocaine
euphoria, sitmulation, NO physical dependence
What are the CV effects of cocaine
increased dopaminergic and adrenergic stimulation, blocking NT re-uptake and increased NE synaptic release, tachycardia, HTN and vascular spasm
leads to MI via constriction
arrythmias via increased SAN
What are the neuro effects of cocaine
hyperpyrexia and seizures
what occurs if cocaine is taken during pregnancy
decreased placental blood flow, fetal hypoxia, neuro deficits and spontaneous abortion
septum perforation is a side effect of what elicit drug
cocaine
What are the side effects of heroin
euphoria, hallucinations, somnolence, sedation, physically addictive
what are the causes of sudden death from heroin
respiratory depression, pulm edema and arrhythmia
Why is tricuspid valve endocarditis common in heroin users
skin flora from injections
what is the renal pathology of ehroin users
amyloidosis, focal segmenteal glomerulosclerosis–> proteinuria, nephrotic syndrome
what are the sideeffects of amphetamines
euphoria, increased CNS dopamine release–> dec glutamate release
what occurs with long term use of amphetamines
violent behavior, confusion, paranoia, hallucinations
what is the main substance in marjuana
THC
what is the mech of THC
binds endogenous cannabinoid R that change the hypothalamic pituitary adrenal axis that regulates appetite, food intake, energy balance, fertility, sexual behavior
what are the bad effects of THC/smoking
bronchitis, pharyngitis, COPD from smoking
What are the Tx benefits of THC
chemotherapy induced nausea and chronic pain syndromes
What is a contusion
blunt force that injures small blood vessels. bleeding without disruption of tissue (bruise)
what is a puncture caused by
long narrow instrument or gunshot
What are the greatest threats to life after a thermal burn
shock, sepsis, respiratory insufficiency
what is are the classificaitons of degree burns
1st degree- superficial contained to epidermis
2nd degree- partial thickness involving dermis
full-thickness extending to subcutaneous tissue
when >20% SA of body is burned what occurs
rapid fluid mobilizations, potential hypovolemic shock
when >40% SA of body is burned what occurs
hypermetabolic state (at least 2x)
What opportunistic infections occur in burn patients
pseudomonas, antibiotic R nosocomial microbes like S aureus and Candida
what is the mech that water soluble gases cause upper airway edema and inflammation. give examples
chlorine, sulfur oxides, ammonia
react with H2O
what are the lipid soluble gases
NO, burning plastic that causes pneumonitis
What are heat cramps assoc with and why
hyperthermia
loss of electrolytes through sweating
what are signs of heat stroke
sweating stops, generalized vasodilation and peripheral pooling of blood, dec ECV
necrosis of mm and myocardium
what causes malignant hyperthermia
changes in the ryanodine receptor type I
What are the symptoms of hypothermia
loss of consciousness, bradycardia, A fib
how do tissues freeze
direct injury by crystallization of IC and EC water
what scenario caused trench foot
hypothermia
what type of skin is more resistant
dry skin because wet skin has less resistance so less heat is generated
What are examples on non-ionizing radiation
UV, infrared light, radio waves, microwaves, sound waves
they do not displace bound electrons
what are examples of ionizing radiation
x rays, y-rays, high energy neutrons, alpha particles and beta particles
can remove electrons
what are the radiation units
Curie Ci
Gray Gy
Sievert Sv
What is a Sievert
biologic effect of particular radiation dose
How is tumor therapy of ionizing radiation given
divided in doses to allow time for the cells to repair. tumor cells do not repair well
what type of tissues are less susceptible to radiation
poorly vascularized tissues with relative hypoxia
what systems are first involved with acute radiation syndrome
hemtopoietic and GI and CNS
what can be the result of high doses of radiation to stem cells
permanent aplastic anemia
when does fibrosis occur after radiation
weeks/months
What type of DNa damage is most severe
ds DNA breaks
require homologous or non homologous recombination
what is the most common ds DNA break repair
non homologous end joining leading to deletions, duplications, inversion and translocations
What type of deficieny occurs in infants only receiving formula
iron deficiency
what is secondary malnutrition
sufficient nutrient supply yet but there is no sufficient intake, malabsorption, impaired utilization or storage, excess loss or increased demand
What is PEM
protein energy malnutrition from inadequate intake of protein and calories of malabsorption
what are sign of PEM
muscle and fat loss, lethargy, weakness BMI<16
What happens in marasmus
muscle mass dec from fortein and fat mobilization from somatic compartment to provide energy
what happens to leptin levels during marasmus
decreased so increases lipolysis thorugh activation of pituitary-adreanl axis production of glucocorticoids
what happens in kwashiorkor
protein deprivation is greater than overall calorie reduction
where is pretin lost form in kwashiorkor
visceral compartment of body, esp the liver
spares mm and adipose
severe edema from hypoalbuminemia
what are signs of kwashiorkor
apathy, listlessness, anorexia, immune deficiency, secondary infecitons are common
What is Cachexia caused by
proteolysis inducing factor PIF and lipid-moblizing factor from inc TNF and IL6 with tuors
what is the role of PIF and cytokines leading to cachexia
skelatal muscle catabolism via NF-kB induced activation of the ubiquitin-proteasome pathway
What is anorexia nervosa
self induced starvation, serotonin levels implicated
What are signs of anorexia nervosa
amennorhea, cold intolerance from dec thyroid hormone as well as brady cardia, constipation, dry skin and hair thinning
bone thinning from dec estrogen levels
what causes sudden death in anorexia nervosa
arrythmias in setting of hypokalemia
What is bulimia
binging followed by induced vomiting
what are the medical complications with bulimia
hypokalemia leading to arrythmias and gastric content aspiration, esophageal gastric lacerations
how many vitamins are necessary for health
9 water soluble
4 fat soluble ADEK
What is the storage and transport form of vit A
retinol
what is the acid form of vit A
retinoic acid
what is the aldehyde form of vit a
retinal
where is most of vit A stored
90% stellate in the liver with a 6 mo reserve
what makes rhodopsin and iodopsin
retinal and membrane opsins
How does Vit A contribute to the mucus secreting epithelial cell differentiation
retinoic acid and IC R (RARs) will form herterodimer with retinoic X R (RXR)
RXR then activates genes via binding promoter regions
What happens with epithelium if vit A deficiency
squamous metaplasia of epithelium
How does retinoic acid affect lipid metabolism
peroxisome proliferator activated R PPARs interact with RXR and regulate lipid metabolism and adipogenesis
What are clinical features of Vit A deficiency
night blindness called xerophthalmia from keratinization of conjunctival and lacrimal epithelium causing xerosis and small opaque spots on cornea from keratin
keratinizing metaplasia of epithelial surface(inc respiratory infections
inc renal and urinary stones from keratinized epithelium desquamation
What are signs of acute Vit A toxicity
acute HA, vomiting, stupor, papilledema
What are signs of chronic Vit A toxicity
weight loss, nausea, vomiting, lip dryness, bone/joint pain(retinoic acid activates osteoclasts)
What transports Vit D
plasma alpha1 globulin
what enzyme converts Vit D to most active form and where is it located
alpha1-hydroxylase in the liver
What induces alpha1 hydroxylase
dec Ca that induces PTH which activates it
also dec Phosphate
What type of membrane R does vit D bind to
IC R that diretly activate protein kinase C and open Ca channels
what does Vit D do to increase/decrease Ca and Pi
induces TRP V6 which increases Ca absorption in gut
induces TRP V5 to increase renal tubular Ca resorption
increases RANKL on osteoblasts to increase osteoclast maturation and activity
increases osteoblast to produce osteocalcin that increases bone mineralization
What are the results from dec Vit D
deficient absorption Ca and Pi hypocalcemia which activates PTH icnreased Ca retention in urine with Pi wasting (dec bone mineralization) rickets in children osteomalacia in adults
what else is Vit D known for besides Ca and Pi regulation
innate immunity
regulates many genes involved
chronic lack of Vit D can lead to what
increase incidence of colon, prostate, and breast CA
What does Vit C activate
prolyl and lysyl hydroxylation of pro collagen which facilitates cross linking
also scavenges free radicals and regenerates antioxidant forms of Vit E
scurvy from inadequate osteoid and hemorhage
Obesity is a BMI of what
> 30
What controls food intake and energy expenditure
the POMC/CART neurons that increase energy expenditure and weight loss by making anorexigenica alpha melanocyte that increases the hormone which binds melanocortin R
NPY/AgRP neurons increase food intake and weight gain
What makes leptin
adipose tissues when fat stores are abundant
what does leptin do
inc POMC/CART and dec NPY/AgRP to dec food intake
also stimualtes physical activity, heat production and energy expenditure
What makes adiponectin
adipocytes
what is the role of adipnectin
dec liver influx of tiglycerides, inc skel muscle fatty acid oxidation
dec hepatic GNG and inc insulin sensitivity
What pro inflammatory cytokines come from adipose tissue
TNF IL6 IL1
what are the gut hormones that affect appetite
ghrelin, PYY and insulin
what is the role of ghrelin
increase food intake via NPT/AgRP
how is ghrelin altered in obesity
post prandial ghrelin suppression is attenuated
When are PYY levels the highest
after meals or after gastric bypass
What is thought to be dec in prader willi patients
PYY
What metabolic syndromes can result from obesity
insuline resistance, HTN and dylipidemia
DMII
the HTN and hypertiglyceremia of obesity can lead to what condition
increased risk coronary artery disease
how does obesity affect liver
nonalcoholic steatohepatitis
what is a very common sequelae of obesity
gall stones, cholelithiasis
What is hypoventialiton syndrome
respiratory changes in obesity that is assoc with hypersomnolence, polycythemia and right sided heart failure
What type of CA are assoc with men BMI>25
esophageal adenocarcinoma
thyroid, colon and kidney CA
what type of CA are assoc with women BMI>25
esophageal adenocarcinoma
endometrial, gallbladder and kidney CA
what is activated during hyperinsulinemia
kinases P3K and RAS
also insulin like GF which can causes mitogenic and apoptotic peptides
how can obesity lead to adrenal and ovarian increases in androgen production
fat cell aromatases increases estrogen form androgen precursors
What does aflatoxin, exogenous carcinogen, cause
hepatocellular carcinoma
what are endogenous carcinogens
from food diet like amides in digested proteins etc
why is a high fiber diet good
bind and removal of potential carcinogens, increases the bowel transit time and dec mucosal exposure to toxic metabolites
What type of diet factors are presumed to be anti-carcinogenic
selenium, Beta carotene, Vit B and E
how are omega 3 FA protective against CV
different spectrum of eicosanoids that fats stimulate
how is caloric restriction dec risk atherosclerosis
sirtuin activation and dec insulin
describe the metabolites from phase I and II reactions
phase I leaves water soluble compounds that are readily excreted
At 40 ug/ml lead what happens in children?
children- decreased Hb synthesis
at 10 ug/ml lead what hapens in children
developmental toxicity, decreased IQ decreased hearing, decreased growth and impaired peripheral nerve function
if you suspect lead poisoning what will you look for in lab results
increased levels of zinc protoporphyrin
the peripheral demyleinating neuropathy seen with lead in adults show what clinical signs
attack most used mm so see wrist drop and foot drop
what are the neuro effects of arsenic poisoning
sensorimotor neuropathy that causes paresthesias, numbness and pain
what is the most serious risk of chronic exposure to arsenic
increased risk for cancer, esp lungs and skin
describe arsenic induce skin tumors
multiple and appear on palms and soles
what do we measure for passive smoke inhalation in nonsmokers
cotinine, a metabolite of nicotine
acute alcoholism affects what first
CNS- subcortical structures like brains stem and reticular formation then affect control centers for respiration
Vit B1 is what
thiamine
what is Vit B3 and deficiency look like
niacin
pellagra- 3 Ds dementia, dermatitis, diarrhea
a deficiency in Vit K presents how
hemorrhagic disease
what is the main part of alcohol that contributes to laryngeal and esophageal cancer
acetaldehyde
A vit A deficiency what infection are you more prone to
measles
What is seen in an infant with Vit E deficiency
dec height and weight
no DTRs
decreased sensory
spinocerebellar degeneration
What is isoniazid
B6 antagonist
pyridoxine
What is Vit B2 and what would deficiency look like
riboflavin
ariboflavinosis, cheilosis, stomatitis, glossitis, dermatitis, corneal vascularization
What does a Vit B12 deficiency look like
megaloblastic pernicious anemia and degeneration of posterolateral spinal cord tracts
what does a deficiency in folate look like
megaloblastic anemia, neural tube defects
Oral contraceptives play a role in cancer development how
reduce incidence of endometrial and ovarian
association though with hepatic adenomas
inhalation of toxic gas will cause death how
pulmonary edema
atropine can be used to counteract what toxic posioning
organophosphates
How do you tell difference marasmus and kwashiorkor
wkashiorkor still in 60% and up weight
exposure to huge amounts of radiation will cause what
cerebral syndrome
What gene is associated with obesity
MC4R
in a full thickness burn what component of skin will you have lost completely
dermal appendages like hair follicles and sweat glands
what is beriberi
thiamine deficiency leading to heart failure
what is more potent crack or cocaine
crack
what are greatest threats to burn victims
chock sepsis and respiratory insufficiency
what type of necrosis occurs with burns
coagulative
radon exposure can lead to what
lung cancers
describe liver and small bowel in kwashiorkor vs marasmus
the liver is enlarged in kwashiorkor and the small bowel shows decreased mitotic index in the glandular crypts
what are the clinical features of a selenium deficiency
myopathy and cardiomyopathy
besides adiponectin and leptin what else does adipose tissue produce
TNF IL6 IL1 and IL18
results in high levels circulating C reactive protein
