Chapter9 Flashcards
1
Q
what is the DALY
A
disabilty adjusted life year, metric that combines yrs lotted to premature mortality and yeras lived with illness and disability
2
Q
what is the leading global cause of health loss in developing countries vs developed
A
developing is undernutrition
coronary/CV in developed
3
Q
5/10 top causes of death
A
infection related
4
Q
what are xenobiotics
A
exogenous environmental agents inhaled, ingested and absorbed
5
Q
what type of compounds readily cross plasma membranes
A
lipophilic compounds with increased blood transport due to lipoproteins
6
Q
What are the 2 groups of drug-metabolizing enzymes
A
phase I: enzyme include hydrolysis, oxidation and reduction
phase II: enzymes include glucuronidation, sulfation, methylation, conjugation
7
Q
What are the main phase I drug metabolizing enzymes
A
cytochrom P450 (CYP) enzymatic activity releases ROS
8
Q
What organ is most affected by outdoor air pollution
A
lungs. dec pulmonary function, increased airway reactivity and infections. dec mucociliary clearance
9
Q
What are the major components of smog at lower atmosphere
A
contains NOs and colatile organic compounds
10
Q
What is the main source of sulfur dioxide in atmosphere
A
coal and oil combustion
copper smelting
paper manufacturing
11
Q
what are the clinical results of sulfur dioxide pollution
A
dyspnea, airway hyperreactivity
12
Q
how come smaller particulate matter is more deleterious to the lungs
A
because the >10 microns are trapped in nasal mucus/upper respiratory tract
13
Q
What does CO cause
A
impaired resp function
acute poisoning: CNS depression and systemic hypoxia and characteristic cherry-red coloring from increased carboxyhemoglobin
14
Q
What type of toxins are in wood smoke
A
carcinogenic polycyclic hydrocarbon
15
Q
What is radon
A
radioactive gas from uranium decay in soil that increases risk in cancer
16
Q
what does fromaldehyde toxicity cause
A
acute aye and upper respiratory irritation
17
Q
Why are children at higher risk for lead poisoning
A
increased GI absorption and increased permeable blood-brain barrier
18
Q
What are the neurological risks of lead poisoning and why
A
competes for Ca ion
in children causes psychomotor impairments
in adults causes peripheral demyelinating neuropathy
19
Q
what are the hemolytic risks of lead poisoning
A
decrease in heme-synthesis enzymes and iron incorporation
leading to microcytic, hypo chromic anemia
20
Q
how does lead poisoning affect bone growth
A
changes the bone healing at epiphyses decreasing bone healing
21
Q
what is lead colic
A
abdominal pain and anorexia
22
Q
Why is the brain susceptible to mercury
A
lipid soluble, CNS accumulations with increased binding affinity for cellular thiol groups
23
Q
what form of arsenic is most toxic
A
ArO3
24
Q
ingestion of arsenic can cause what
A
GI, CV and neurosequalae via dec mitochondrial ox-phos
25
What occurs with ingestion of Cadmium
skeltal changes due to Ca loss
26
how does cadmium poisoning lead to obstructive lung disease and renal tubular damage
alveolar Macrophage necrosis
27
Why does cadmium cause an increase in lung cancer
from dNA damage induced by ROS
28
What does chloroform toxicity cause
acute CNS depression, liver and kidney toxicity
29
aromatic hydrocarbons like benzene are metabolized how and cause what
CYP2E1 and the toxic metabolites disrupt marrow hematopoiesis with increased risk of AML
30
what is released from fossil fuel combustion and what does it cause
polycyclic hydrocarbons
| increased risk of lung and bladder CA
31
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
32
What can hapen from toxic mineral dust inhalation
chronic, non-neoplastic diffusely fibrosing pneumoconiosis
33
What occurs with vinyl chloride toxication
angiosarcoma of liver
34
what can occur with phthalate toxication
endocrine disruption, testicular dysgenesis syndrome
35
What is the mechanism of nicotine and what does it cause
binds CNS R releasing catecholamines that increase HR< BP and cardiac contractility
36
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
37
what are other Dx from smoking
tracheobronchial inflammation
bronchitis
emphysema from elastase production
atherosclerosis, MI from platelet aggreagation, endothelial dysfunction, myocardial hypoxia
38
What can maternal- smoking cause
fetal hypoxia with decreased intrauterine growth and increased spontaneous abortion, increased change preterm birth
39
at what level of alcohol causes drowsiness? stupor?
drowsy at 200 mg/dL
stupor at 300
coma at levels above
40
How do chronic alcoholics have increased tolerance to alcohol
hepatic CYP induction
41
how is EtOH metabolized
acetaldehyde via cytosolic ADH
42
What does hepatic acetaldehyde dehydrogenase do
convert acetaldehyde to acetate used by mitochondria
43
What CYP does alcohol require for metabolism
CYP2E1
44
What occurs in people with an inactive copy of the ALDH enzyme
1/2 asians, they cannot oxidize acetaldehyde
| nausea, flushing, tachycardia, hyperventilation
45
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
46
What happens with EtOH in the GI tract
endotoxin release from gut flora with inflammatory cytokine production
47
What are signs of acute alcohol injury
heaptic steatosis, gastritis and ulceration, CNS depression
48
What are the liver changes in chronic alcoholism
fatty change, alcoholic hepatitis, cirrhosis assoc
| portal HTN and risk for hepatocellular carcinoma
49
What are the GI changes in chronic alcoholism
massive bleeding due to acute gastritis and ulceration or esophageal varices from portal HTN
50
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
51
what are the heart effects from chronic alcoholism
dilated cardiomyopathy assoc with increased HTN incidence, inc EtOH, dec liver HDL
52
what are the pancreatic effects from chronic alcoholism
increase risk of acute and chronic pancreatitis
53
How does chronic alcoholism affect fetal growth
developmental defects, consumption during first trimester is most harmful
54
What type of CA are associated with chronic alcoholism
oral cavity, pharynx, esophagus, liver, possibly breast due to acetaldehyde metabolite
55
What are sirtuins
histone deacetylases
56
What is the catch 22 of Hormone replacement therapy
alleviates menopausal Sx, dec osteoporosis
| increased risk of breast CA and thromboembolism
57
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
58
what is a risk factor for someone that owudl prevent them from taking oral contraceptives
factor V or prothrombin mutation carriers
59
How does synthetic testosterone lead to testicular atrophy and gynecomastia in men, virilizaiton in women
increase dose feedback so decreased LH and FSH production
60
What drug is responsible for 50% acute liver failure in US
acetominophen
61
What metabolizes acetaminophen
phase II hepatic enzymes mainly
| then CYP2E---> NAPQ1 conjugated with glutathione
62
how does increased acetaminophen affect liver
glutathione depletion, ROS injury, inc NAPQ1 complexes with hepatocyte membrane proteins and mitochondria causing degradation
63
what are th symptoms of aspirin overdose
respiratory alkylosis-->metabolic acidosis
64
what are the symptoms of chronic aspirin toxicity
HA, dizzyness, tinnitus, mental confusion, drowsiness, nausea, vomiting, diarrhea
65
what can cause renal papillary necrosis
long-term ingestion of aspirin and phenacetin mix
66
What are the sideeffects of cocaine
euphoria, sitmulation, NO physical dependence
67
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
68
What are the neuro effects of cocaine
hyperpyrexia and seizures
69
what occurs if cocaine is taken during pregnancy
decreased placental blood flow, fetal hypoxia, neuro deficits and spontaneous abortion
70
septum perforation is a side effect of what elicit drug
cocaine
71
What are the side effects of heroin
euphoria, hallucinations, somnolence, sedation, physically addictive
72
what are the causes of sudden death from heroin
respiratory depression, pulm edema and arrhythmia
73
Why is tricuspid valve endocarditis common in heroin users
skin flora from injections
74
what is the renal pathology of ehroin users
amyloidosis, focal segmenteal glomerulosclerosis--> proteinuria, nephrotic syndrome
75
what are the sideeffects of amphetamines
euphoria, increased CNS dopamine release--> dec glutamate release
76
what occurs with long term use of amphetamines
violent behavior, confusion, paranoia, hallucinations
77
what is the main substance in marjuana
THC
78
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
79
what are the bad effects of THC/smoking
bronchitis, pharyngitis, COPD from smoking
80
What are the Tx benefits of THC
chemotherapy induced nausea and chronic pain syndromes
81
What is a contusion
blunt force that injures small blood vessels. bleeding without disruption of tissue (bruise)
82
what is a puncture caused by
long narrow instrument or gunshot
83
What are the greatest threats to life after a thermal burn
shock, sepsis, respiratory insufficiency
84
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
85
when >20% SA of body is burned what occurs
rapid fluid mobilizations, potential hypovolemic shock
86
when >40% SA of body is burned what occurs
hypermetabolic state (at least 2x)
87
What opportunistic infections occur in burn patients
pseudomonas, antibiotic R nosocomial microbes like S aureus and Candida
88
what is the mech that water soluble gases cause upper airway edema and inflammation. give examples
chlorine, sulfur oxides, ammonia
| react with H2O
89
what are the lipid soluble gases
NO, burning plastic that causes pneumonitis
90
What are heat cramps assoc with and why
hyperthermia
| loss of electrolytes through sweating
91
what are signs of heat stroke
sweating stops, generalized vasodilation and peripheral pooling of blood, dec ECV
necrosis of mm and myocardium
92
what causes malignant hyperthermia
changes in the ryanodine receptor type I
93
What are the symptoms of hypothermia
loss of consciousness, bradycardia, A fib
94
how do tissues freeze
direct injury by crystallization of IC and EC water
95
what scenario caused trench foot
hypothermia
96
what type of skin is more resistant
dry skin because wet skin has less resistance so less heat is generated
97
What are examples on non-ionizing radiation
UV, infrared light, radio waves, microwaves, sound waves
| they do not displace bound electrons
98
what are examples of ionizing radiation
x rays, y-rays, high energy neutrons, alpha particles and beta particles
can remove electrons
99
what are the radiation units
Curie Ci
Gray Gy
Sievert Sv
100
What is a Sievert
biologic effect of particular radiation dose
101
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
102
what type of tissues are less susceptible to radiation
poorly vascularized tissues with relative hypoxia
103
what systems are first involved with acute radiation syndrome
hemtopoietic and GI and CNS
104
what can be the result of high doses of radiation to stem cells
permanent aplastic anemia
105
when does fibrosis occur after radiation
weeks/months
106
What type of DNa damage is most severe
ds DNA breaks
| require homologous or non homologous recombination
107
what is the most common ds DNA break repair
non homologous end joining leading to deletions, duplications, inversion and translocations
108
What type of deficieny occurs in infants only receiving formula
iron deficiency
109
what is secondary malnutrition
sufficient nutrient supply yet but there is no sufficient intake, malabsorption, impaired utilization or storage, excess loss or increased demand
110
What is PEM
protein energy malnutrition from inadequate intake of protein and calories of malabsorption
111
what are sign of PEM
muscle and fat loss, lethargy, weakness BMI<16
112
What happens in marasmus
muscle mass dec from fortein and fat mobilization from somatic compartment to provide energy
113
what happens to leptin levels during marasmus
decreased so increases lipolysis thorugh activation of pituitary-adreanl axis production of glucocorticoids
114
what happens in kwashiorkor
protein deprivation is greater than overall calorie reduction
115
where is pretin lost form in kwashiorkor
visceral compartment of body, esp the liver
spares mm and adipose
severe edema from hypoalbuminemia
116
what are signs of kwashiorkor
apathy, listlessness, anorexia, immune deficiency, secondary infecitons are common
117
What is Cachexia caused by
proteolysis inducing factor PIF and lipid-moblizing factor from inc TNF and IL6 with tuors
118
what is the role of PIF and cytokines leading to cachexia
skelatal muscle catabolism via NF-kB induced activation of the ubiquitin-proteasome pathway
119
What is anorexia nervosa
self induced starvation, serotonin levels implicated
120
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
121
what causes sudden death in anorexia nervosa
arrythmias in setting of hypokalemia
122
What is bulimia
binging followed by induced vomiting
123
what are the medical complications with bulimia
hypokalemia leading to arrythmias and gastric content aspiration, esophageal gastric lacerations
124
how many vitamins are necessary for health
9 water soluble
| 4 fat soluble ADEK
125
What is the storage and transport form of vit A
retinol
126
what is the acid form of vit A
retinoic acid
127
what is the aldehyde form of vit a
retinal
128
where is most of vit A stored
90% stellate in the liver with a 6 mo reserve
129
what makes rhodopsin and iodopsin
retinal and membrane opsins
130
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
131
What happens with epithelium if vit A deficiency
squamous metaplasia of epithelium
132
How does retinoic acid affect lipid metabolism
peroxisome proliferator activated R PPARs interact with RXR and regulate lipid metabolism and adipogenesis
133
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
134
What are signs of acute Vit A toxicity
acute HA, vomiting, stupor, papilledema
135
What are signs of chronic Vit A toxicity
weight loss, nausea, vomiting, lip dryness, bone/joint pain(retinoic acid activates osteoclasts)
136
What transports Vit D
plasma alpha1 globulin
137
what enzyme converts Vit D to most active form and where is it located
alpha1-hydroxylase in the liver
138
What induces alpha1 hydroxylase
dec Ca that induces PTH which activates it
| also dec Phosphate
139
What type of membrane R does vit D bind to
IC R that diretly activate protein kinase C and open Ca channels
140
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
141
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
```
142
what else is Vit D known for besides Ca and Pi regulation
innate immunity
| regulates many genes involved
143
chronic lack of Vit D can lead to what
increase incidence of colon, prostate, and breast CA
144
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
145
Obesity is a BMI of what
>30
146
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
147
What makes leptin
adipose tissues when fat stores are abundant
148
what does leptin do
inc POMC/CART and dec NPY/AgRP to dec food intake
| also stimualtes physical activity, heat production and energy expenditure
149
What makes adiponectin
adipocytes
150
what is the role of adipnectin
dec liver influx of tiglycerides, inc skel muscle fatty acid oxidation
dec hepatic GNG and inc insulin sensitivity
151
What pro inflammatory cytokines come from adipose tissue
TNF IL6 IL1
152
what are the gut hormones that affect appetite
ghrelin, PYY and insulin
153
what is the role of ghrelin
increase food intake via NPT/AgRP
154
how is ghrelin altered in obesity
post prandial ghrelin suppression is attenuated
155
When are PYY levels the highest
after meals or after gastric bypass
156
What is thought to be dec in prader willi patients
PYY
157
What metabolic syndromes can result from obesity
insuline resistance, HTN and dylipidemia
| DMII
158
the HTN and hypertiglyceremia of obesity can lead to what condition
increased risk coronary artery disease
159
how does obesity affect liver
nonalcoholic steatohepatitis
160
what is a very common sequelae of obesity
gall stones, cholelithiasis
161
What is hypoventialiton syndrome
respiratory changes in obesity that is assoc with hypersomnolence, polycythemia and right sided heart failure
162
What type of CA are assoc with men BMI>25
esophageal adenocarcinoma
| thyroid, colon and kidney CA
163
what type of CA are assoc with women BMI>25
esophageal adenocarcinoma
| endometrial, gallbladder and kidney CA
164
what is activated during hyperinsulinemia
kinases P3K and RAS
| also insulin like GF which can causes mitogenic and apoptotic peptides
165
how can obesity lead to adrenal and ovarian increases in androgen production
fat cell aromatases increases estrogen form androgen precursors
166
What does aflatoxin, exogenous carcinogen, cause
hepatocellular carcinoma
167
what are endogenous carcinogens
from food diet like amides in digested proteins etc
168
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
169
What type of diet factors are presumed to be anti-carcinogenic
selenium, Beta carotene, Vit B and E
170
how are omega 3 FA protective against CV
different spectrum of eicosanoids that fats stimulate
171
how is caloric restriction dec risk atherosclerosis
sirtuin activation and dec insulin
172
describe the metabolites from phase I and II reactions
phase I leaves water soluble compounds that are readily excreted
173
At 40 ug/ml lead what happens in children?
children- decreased Hb synthesis
174
at 10 ug/ml lead what hapens in children
developmental toxicity, decreased IQ decreased hearing, decreased growth and impaired peripheral nerve function
175
if you suspect lead poisoning what will you look for in lab results
increased levels of zinc protoporphyrin
176
the peripheral demyleinating neuropathy seen with lead in adults show what clinical signs
attack most used mm so see wrist drop and foot drop
177
what are the neuro effects of arsenic poisoning
sensorimotor neuropathy that causes paresthesias, numbness and pain
178
what is the most serious risk of chronic exposure to arsenic
increased risk for cancer, esp lungs and skin
179
describe arsenic induce skin tumors
multiple and appear on palms and soles
180
what do we measure for passive smoke inhalation in nonsmokers
cotinine, a metabolite of nicotine
181
acute alcoholism affects what first
CNS- subcortical structures like brains stem and reticular formation then affect control centers for respiration
182
Vit B1 is what
thiamine
183
what is Vit B3 and deficiency look like
niacin
| pellagra- 3 Ds dementia, dermatitis, diarrhea
184
a deficiency in Vit K presents how
hemorrhagic disease
185
what is the main part of alcohol that contributes to laryngeal and esophageal cancer
acetaldehyde
186
A vit A deficiency what infection are you more prone to
measles
187
What is seen in an infant with Vit E deficiency
dec height and weight
no DTRs
decreased sensory
spinocerebellar degeneration
188
What is isoniazid
B6 antagonist
| pyridoxine
189
What is Vit B2 and what would deficiency look like
riboflavin
| ariboflavinosis, cheilosis, stomatitis, glossitis, dermatitis, corneal vascularization
190
What does a Vit B12 deficiency look like
megaloblastic pernicious anemia and degeneration of posterolateral spinal cord tracts
191
what does a deficiency in folate look like
megaloblastic anemia, neural tube defects
192
Oral contraceptives play a role in cancer development how
reduce incidence of endometrial and ovarian
| association though with hepatic adenomas
193
inhalation of toxic gas will cause death how
pulmonary edema
194
atropine can be used to counteract what toxic posioning
organophosphates
195
How do you tell difference marasmus and kwashiorkor
wkashiorkor still in 60% and up weight
196
exposure to huge amounts of radiation will cause what
cerebral syndrome
197
What gene is associated with obesity
MC4R
198
in a full thickness burn what component of skin will you have lost completely
dermal appendages like hair follicles and sweat glands
199
what is beriberi
thiamine deficiency leading to heart failure
200
what is more potent crack or cocaine
crack
201
what are greatest threats to burn victims
chock sepsis and respiratory insufficiency
202
what type of necrosis occurs with burns
coagulative
203
radon exposure can lead to what
lung cancers
204
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
205
what are the clinical features of a selenium deficiency
myopathy and cardiomyopathy
206
besides adiponectin and leptin what else does adipose tissue produce
TNF IL6 IL1 and IL18
| results in high levels circulating C reactive protein
