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Patho II > Chapter9 > Flashcards

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

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2
Q

what is the leading global cause of health loss in developing countries vs developed

A

developing is undernutrition

coronary/CV in developed

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3
Q

5/10 top causes of death

A

infection related

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4
Q

what are xenobiotics

A

exogenous environmental agents inhaled, ingested and absorbed

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5
Q

what type of compounds readily cross plasma membranes

A

lipophilic compounds with increased blood transport due to lipoproteins

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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

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7
Q

What are the main phase I drug metabolizing enzymes

A 
cytochrom P450 (CYP)
enzymatic activity releases ROS
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8
Q

What organ is most affected by outdoor air pollution

A

lungs. dec pulmonary function, increased airway reactivity and infections. dec mucociliary clearance

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9
Q

What are the major components of smog at lower atmosphere

A

contains NOs and colatile organic compounds

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10
Q

What is the main source of sulfur dioxide in atmosphere

A

coal and oil combustion
copper smelting
paper manufacturing

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11
Q

what are the clinical results of sulfur dioxide pollution

A

dyspnea, airway hyperreactivity

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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

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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

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14
Q

What type of toxins are in wood smoke

A

carcinogenic polycyclic hydrocarbon

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15
Q

What is radon

A

radioactive gas from uranium decay in soil that increases risk in cancer

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16
Q

what does fromaldehyde toxicity cause

A

acute aye and upper respiratory irritation

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17
Q

Why are children at higher risk for lead poisoning

A

increased GI absorption and increased permeable blood-brain barrier

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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

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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

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20
Q

how does lead poisoning affect bone growth

A

changes the bone healing at epiphyses decreasing bone healing

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21
Q

what is lead colic

A

abdominal pain and anorexia

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22
Q

Why is the brain susceptible to mercury

A

lipid soluble, CNS accumulations with increased binding affinity for cellular thiol groups

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23
Q

what form of arsenic is most toxic

A

ArO3

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24
Q

ingestion of arsenic can cause what

A

GI, CV and neurosequalae via dec mitochondrial ox-phos

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25
Q

What occurs with ingestion of Cadmium

A

skeltal changes due to Ca loss

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26
Q

how does cadmium poisoning lead to obstructive lung disease and renal tubular damage

A

alveolar Macrophage necrosis

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27
Q

Why does cadmium cause an increase in lung cancer

A

from dNA damage induced by ROS

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28
Q

What does chloroform toxicity cause

A

acute CNS depression, liver and kidney toxicity

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29
Q

aromatic hydrocarbons like benzene are metabolized how and cause what

A

CYP2E1 and the toxic metabolites disrupt marrow hematopoiesis with increased risk of AML

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30
Q

what is released from fossil fuel combustion and what does it cause

A

polycyclic hydrocarbons

increased risk of lung and bladder CA

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31
Q

What are pesticides like DDT and non-pesticides like PCB and dioxin? What do they cause

A

organochlorines
DDT causes endocrine disruption with anti-estrogenic/androgenic effects
Dioxin and PCB cause folliculitis, dermatosis, hepatic and CNS alterations activating CYP

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32
Q

What can hapen from toxic mineral dust inhalation

A

chronic, non-neoplastic diffusely fibrosing pneumoconiosis

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33
Q

What occurs with vinyl chloride toxication

A

angiosarcoma of liver

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34
Q

what can occur with phthalate toxication

A

endocrine disruption, testicular dysgenesis syndrome

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35
Q

What is the mechanism of nicotine and what does it cause

A

binds CNS R releasing catecholamines that increase HR< BP and cardiac contractility

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36
Q

What causing Cancer from smoking

A

carcinogenic polycylic hydrocarbons, benzopyrene, nitosamines in smoke
CYP modification increases carcinogenicity in lung, oral cavity, esophagus, pancreas, bladder, laryngeal CA

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37
Q

what are other Dx from smoking

A

tracheobronchial inflammation
bronchitis
emphysema from elastase production
atherosclerosis, MI from platelet aggreagation, endothelial dysfunction, myocardial hypoxia

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38
Q

What can maternal- smoking cause

A

fetal hypoxia with decreased intrauterine growth and increased spontaneous abortion, increased change preterm birth

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39
Q

at what level of alcohol causes drowsiness? stupor?

A

drowsy at 200 mg/dL
stupor at 300
coma at levels above

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40
Q

How do chronic alcoholics have increased tolerance to alcohol

A

hepatic CYP induction

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41
Q

how is EtOH metabolized

A

acetaldehyde via cytosolic ADH

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42
Q

What does hepatic acetaldehyde dehydrogenase do

A

convert acetaldehyde to acetate used by mitochondria

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43
Q

What CYP does alcohol require for metabolism

A

CYP2E1

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44
Q

What occurs in people with an inactive copy of the ALDH enzyme

A

1/2 asians, they cannot oxidize acetaldehyde

nausea, flushing, tachycardia, hyperventilation

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45
Q

why does the liver accumulate fat from alcohol

A

ADH oxidation of EtOH reduces NAD to NADH and NAD is required for fatty acid oxidation and lactic acid to pyruvate

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46
Q

What happens with EtOH in the GI tract

A

endotoxin release from gut flora with inflammatory cytokine production

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47
Q

What are signs of acute alcohol injury

A

heaptic steatosis, gastritis and ulceration, CNS depression

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48
Q

What are the liver changes in chronic alcoholism

A

fatty change, alcoholic hepatitis, cirrhosis assoc

portal HTN and risk for hepatocellular carcinoma

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49
Q

What are the GI changes in chronic alcoholism

A

massive bleeding due to acute gastritis and ulceration or esophageal varices from portal HTN

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50
Q

How does chronic alcoholism affect the brain

A

thiamine deficiency from poor nutrition can lead to peripheral neuropathy, Wernicke-Korsakoff syndrome, cerebral atrophy, cerebellar degeneration, optic neuropathy

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51
Q

what are the heart effects from chronic alcoholism

A

dilated cardiomyopathy assoc with increased HTN incidence, inc EtOH, dec liver HDL

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52
Q

what are the pancreatic effects from chronic alcoholism

A

increase risk of acute and chronic pancreatitis

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53
Q

How does chronic alcoholism affect fetal growth

A

developmental defects, consumption during first trimester is most harmful

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54
Q

What type of CA are associated with chronic alcoholism

A

oral cavity, pharynx, esophagus, liver, possibly breast due to acetaldehyde metabolite

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55
Q

What are sirtuins

A

histone deacetylases

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56
Q

What is the catch 22 of Hormone replacement therapy

A

alleviates menopausal Sx, dec osteoporosis

increased risk of breast CA and thromboembolism

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57
Q

What are the risks of oral contraceptives

A

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

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58
Q

what is a risk factor for someone that owudl prevent them from taking oral contraceptives

A

factor V or prothrombin mutation carriers

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59
Q

How does synthetic testosterone lead to testicular atrophy and gynecomastia in men, virilizaiton in women

A

increase dose feedback so decreased LH and FSH production

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60
Q

What drug is responsible for 50% acute liver failure in US

A

acetominophen

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61
Q

What metabolizes acetaminophen

A

phase II hepatic enzymes mainly

then CYP2E—> NAPQ1 conjugated with glutathione

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62
Q

how does increased acetaminophen affect liver

A

glutathione depletion, ROS injury, inc NAPQ1 complexes with hepatocyte membrane proteins and mitochondria causing degradation

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63
Q

what are th symptoms of aspirin overdose

A

respiratory alkylosis–>metabolic acidosis

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64
Q

what are the symptoms of chronic aspirin toxicity

A

HA, dizzyness, tinnitus, mental confusion, drowsiness, nausea, vomiting, diarrhea

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65
Q

what can cause renal papillary necrosis

A

long-term ingestion of aspirin and phenacetin mix

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66
Q

What are the sideeffects of cocaine

A

euphoria, sitmulation, NO physical dependence

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67
Q

What are the CV effects of cocaine

A

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

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68
Q

What are the neuro effects of cocaine

A

hyperpyrexia and seizures

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69
Q

what occurs if cocaine is taken during pregnancy

A

decreased placental blood flow, fetal hypoxia, neuro deficits and spontaneous abortion

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70
Q

septum perforation is a side effect of what elicit drug

A

cocaine

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71
Q

What are the side effects of heroin

A

euphoria, hallucinations, somnolence, sedation, physically addictive

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72
Q

what are the causes of sudden death from heroin

A

respiratory depression, pulm edema and arrhythmia

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73
Q

Why is tricuspid valve endocarditis common in heroin users

A

skin flora from injections

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74
Q

what is the renal pathology of ehroin users

A

amyloidosis, focal segmenteal glomerulosclerosis–> proteinuria, nephrotic syndrome

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75
Q

what are the sideeffects of amphetamines

A

euphoria, increased CNS dopamine release–> dec glutamate release

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76
Q

what occurs with long term use of amphetamines

A

violent behavior, confusion, paranoia, hallucinations

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77
Q

what is the main substance in marjuana

A

THC

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78
Q

what is the mech of THC

A

binds endogenous cannabinoid R that change the hypothalamic pituitary adrenal axis that regulates appetite, food intake, energy balance, fertility, sexual behavior

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79
Q

what are the bad effects of THC/smoking

A

bronchitis, pharyngitis, COPD from smoking

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80
Q

What are the Tx benefits of THC

A

chemotherapy induced nausea and chronic pain syndromes

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81
Q

What is a contusion

A

blunt force that injures small blood vessels. bleeding without disruption of tissue (bruise)

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82
Q

what is a puncture caused by

A

long narrow instrument or gunshot

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83
Q

What are the greatest threats to life after a thermal burn

A

shock, sepsis, respiratory insufficiency

84
Q

what is are the classificaitons of degree burns

A

1st degree- superficial contained to epidermis
2nd degree- partial thickness involving dermis
full-thickness extending to subcutaneous tissue

85
Q

when >20% SA of body is burned what occurs

A

rapid fluid mobilizations, potential hypovolemic shock

86
Q

when >40% SA of body is burned what occurs

A

hypermetabolic state (at least 2x)

87
Q

What opportunistic infections occur in burn patients

A

pseudomonas, antibiotic R nosocomial microbes like S aureus and Candida

88
Q

what is the mech that water soluble gases cause upper airway edema and inflammation. give examples

A

chlorine, sulfur oxides, ammonia

react with H2O

89
Q

what are the lipid soluble gases

A

NO, burning plastic that causes pneumonitis

90
Q

What are heat cramps assoc with and why

A

hyperthermia

loss of electrolytes through sweating

91
Q

what are signs of heat stroke

A

sweating stops, generalized vasodilation and peripheral pooling of blood, dec ECV
necrosis of mm and myocardium

92
Q

what causes malignant hyperthermia

A

changes in the ryanodine receptor type I

93
Q

What are the symptoms of hypothermia

A

loss of consciousness, bradycardia, A fib

94
Q

how do tissues freeze

A

direct injury by crystallization of IC and EC water

95
Q

what scenario caused trench foot

A

hypothermia

96
Q

what type of skin is more resistant

A

dry skin because wet skin has less resistance so less heat is generated

97
Q

What are examples on non-ionizing radiation

A

UV, infrared light, radio waves, microwaves, sound waves

they do not displace bound electrons

98
Q

what are examples of ionizing radiation

A

x rays, y-rays, high energy neutrons, alpha particles and beta particles
can remove electrons

99
Q

what are the radiation units

A

Curie Ci
Gray Gy
Sievert Sv

100
Q

What is a Sievert

A

biologic effect of particular radiation dose

101
Q

How is tumor therapy of ionizing radiation given

A

divided in doses to allow time for the cells to repair. tumor cells do not repair well

102
Q

what type of tissues are less susceptible to radiation

A

poorly vascularized tissues with relative hypoxia

103
Q

what systems are first involved with acute radiation syndrome

A

hemtopoietic and GI and CNS

104
Q

what can be the result of high doses of radiation to stem cells

A

permanent aplastic anemia

105
Q

when does fibrosis occur after radiation

A

weeks/months

106
Q

What type of DNa damage is most severe

A

ds DNA breaks

require homologous or non homologous recombination

107
Q

what is the most common ds DNA break repair

A

non homologous end joining leading to deletions, duplications, inversion and translocations

108
Q

What type of deficieny occurs in infants only receiving formula

A

iron deficiency

109
Q

what is secondary malnutrition

A

sufficient nutrient supply yet but there is no sufficient intake, malabsorption, impaired utilization or storage, excess loss or increased demand

110
Q

What is PEM

A

protein energy malnutrition from inadequate intake of protein and calories of malabsorption

111
Q

what are sign of PEM

A

muscle and fat loss, lethargy, weakness BMI<16

112
Q

What happens in marasmus

A

muscle mass dec from fortein and fat mobilization from somatic compartment to provide energy

113
Q

what happens to leptin levels during marasmus

A

decreased so increases lipolysis thorugh activation of pituitary-adreanl axis production of glucocorticoids

114
Q

what happens in kwashiorkor

A

protein deprivation is greater than overall calorie reduction

115
Q

where is pretin lost form in kwashiorkor

A

visceral compartment of body, esp the liver
spares mm and adipose
severe edema from hypoalbuminemia

116
Q

what are signs of kwashiorkor

A

apathy, listlessness, anorexia, immune deficiency, secondary infecitons are common

117
Q

What is Cachexia caused by

A

proteolysis inducing factor PIF and lipid-moblizing factor from inc TNF and IL6 with tuors

118
Q

what is the role of PIF and cytokines leading to cachexia

A

skelatal muscle catabolism via NF-kB induced activation of the ubiquitin-proteasome pathway

119
Q

What is anorexia nervosa

A

self induced starvation, serotonin levels implicated

120
Q

What are signs of anorexia nervosa

A

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
Q

what causes sudden death in anorexia nervosa

A

arrythmias in setting of hypokalemia

122
Q

What is bulimia

A

binging followed by induced vomiting

123
Q

what are the medical complications with bulimia

A

hypokalemia leading to arrythmias and gastric content aspiration, esophageal gastric lacerations

124
Q

how many vitamins are necessary for health

A

9 water soluble

4 fat soluble ADEK

125
Q

What is the storage and transport form of vit A

A

retinol

126
Q

what is the acid form of vit A

A

retinoic acid

127
Q

what is the aldehyde form of vit a

A

retinal

128
Q

where is most of vit A stored

A

90% stellate in the liver with a 6 mo reserve

129
Q

what makes rhodopsin and iodopsin

A

retinal and membrane opsins

130
Q

How does Vit A contribute to the mucus secreting epithelial cell differentiation

A

retinoic acid and IC R (RARs) will form herterodimer with retinoic X R (RXR)
RXR then activates genes via binding promoter regions

131
Q

What happens with epithelium if vit A deficiency

A

squamous metaplasia of epithelium

132
Q

How does retinoic acid affect lipid metabolism

A

peroxisome proliferator activated R PPARs interact with RXR and regulate lipid metabolism and adipogenesis

133
Q

What are clinical features of Vit A deficiency

A

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
Q

What are signs of acute Vit A toxicity

A

acute HA, vomiting, stupor, papilledema

135
Q

What are signs of chronic Vit A toxicity

A

weight loss, nausea, vomiting, lip dryness, bone/joint pain(retinoic acid activates osteoclasts)

136
Q

What transports Vit D

A

plasma alpha1 globulin

137
Q

what enzyme converts Vit D to most active form and where is it located

A

alpha1-hydroxylase in the liver

138
Q

What induces alpha1 hydroxylase

A

dec Ca that induces PTH which activates it

also dec Phosphate

139
Q

What type of membrane R does vit D bind to

A

IC R that diretly activate protein kinase C and open Ca channels

140
Q

what does Vit D do to increase/decrease Ca and Pi

A

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
Q

What are the results from dec Vit D

A 
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
Q

what else is Vit D known for besides Ca and Pi regulation

A

innate immunity

regulates many genes involved

143
Q

chronic lack of Vit D can lead to what

A

increase incidence of colon, prostate, and breast CA

144
Q

What does Vit C activate

A

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
Q

Obesity is a BMI of what

A

> 30

146
Q

What controls food intake and energy expenditure

A

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
Q

What makes leptin

A

adipose tissues when fat stores are abundant

148
Q

what does leptin do

A

inc POMC/CART and dec NPY/AgRP to dec food intake

also stimualtes physical activity, heat production and energy expenditure

149
Q

What makes adiponectin

A

adipocytes

150
Q

what is the role of adipnectin

A

dec liver influx of tiglycerides, inc skel muscle fatty acid oxidation
dec hepatic GNG and inc insulin sensitivity

151
Q

What pro inflammatory cytokines come from adipose tissue

A

TNF IL6 IL1

152
Q

what are the gut hormones that affect appetite

A

ghrelin, PYY and insulin

153
Q

what is the role of ghrelin

A

increase food intake via NPT/AgRP

154
Q

how is ghrelin altered in obesity

A

post prandial ghrelin suppression is attenuated

155
Q

When are PYY levels the highest

A

after meals or after gastric bypass

156
Q

What is thought to be dec in prader willi patients

A

PYY

157
Q

What metabolic syndromes can result from obesity

A

insuline resistance, HTN and dylipidemia

DMII

158
Q

the HTN and hypertiglyceremia of obesity can lead to what condition

A

increased risk coronary artery disease

159
Q

how does obesity affect liver

A

nonalcoholic steatohepatitis

160
Q

what is a very common sequelae of obesity

A

gall stones, cholelithiasis

161
Q

What is hypoventialiton syndrome

A

respiratory changes in obesity that is assoc with hypersomnolence, polycythemia and right sided heart failure

162
Q

What type of CA are assoc with men BMI>25

A

esophageal adenocarcinoma

thyroid, colon and kidney CA

163
Q

what type of CA are assoc with women BMI>25

A

esophageal adenocarcinoma

endometrial, gallbladder and kidney CA

164
Q

what is activated during hyperinsulinemia

A

kinases P3K and RAS

also insulin like GF which can causes mitogenic and apoptotic peptides

165
Q

how can obesity lead to adrenal and ovarian increases in androgen production

A

fat cell aromatases increases estrogen form androgen precursors

166
Q

What does aflatoxin, exogenous carcinogen, cause

A

hepatocellular carcinoma

167
Q

what are endogenous carcinogens

A

from food diet like amides in digested proteins etc

168
Q

why is a high fiber diet good

A

bind and removal of potential carcinogens, increases the bowel transit time and dec mucosal exposure to toxic metabolites

169
Q

What type of diet factors are presumed to be anti-carcinogenic

A

selenium, Beta carotene, Vit B and E

170
Q

how are omega 3 FA protective against CV

A

different spectrum of eicosanoids that fats stimulate

171
Q

how is caloric restriction dec risk atherosclerosis

A

sirtuin activation and dec insulin

172
Q

describe the metabolites from phase I and II reactions

A

phase I leaves water soluble compounds that are readily excreted

173
Q

At 40 ug/ml lead what happens in children?

A

children- decreased Hb synthesis

174
Q

at 10 ug/ml lead what hapens in children

A

developmental toxicity, decreased IQ decreased hearing, decreased growth and impaired peripheral nerve function

175
Q

if you suspect lead poisoning what will you look for in lab results

A

increased levels of zinc protoporphyrin

176
Q

the peripheral demyleinating neuropathy seen with lead in adults show what clinical signs

A

attack most used mm so see wrist drop and foot drop

177
Q

what are the neuro effects of arsenic poisoning

A

sensorimotor neuropathy that causes paresthesias, numbness and pain

178
Q

what is the most serious risk of chronic exposure to arsenic

A

increased risk for cancer, esp lungs and skin

179
Q

describe arsenic induce skin tumors

A

multiple and appear on palms and soles

180
Q

what do we measure for passive smoke inhalation in nonsmokers

A

cotinine, a metabolite of nicotine

181
Q

acute alcoholism affects what first

A

CNS- subcortical structures like brains stem and reticular formation then affect control centers for respiration

182
Q

Vit B1 is what

A

thiamine

183
Q

what is Vit B3 and deficiency look like

A

niacin

pellagra- 3 Ds dementia, dermatitis, diarrhea

184
Q

a deficiency in Vit K presents how

A

hemorrhagic disease

185
Q

what is the main part of alcohol that contributes to laryngeal and esophageal cancer

A

acetaldehyde

186
Q

A vit A deficiency what infection are you more prone to

A

measles

187
Q

What is seen in an infant with Vit E deficiency

A

dec height and weight
no DTRs
decreased sensory
spinocerebellar degeneration

188
Q

What is isoniazid

A

B6 antagonist

pyridoxine

189
Q

What is Vit B2 and what would deficiency look like

A

riboflavin

ariboflavinosis, cheilosis, stomatitis, glossitis, dermatitis, corneal vascularization

190
Q

What does a Vit B12 deficiency look like

A

megaloblastic pernicious anemia and degeneration of posterolateral spinal cord tracts

191
Q

what does a deficiency in folate look like

A

megaloblastic anemia, neural tube defects

192
Q

Oral contraceptives play a role in cancer development how

A

reduce incidence of endometrial and ovarian

association though with hepatic adenomas

193
Q

inhalation of toxic gas will cause death how

A

pulmonary edema

194
Q

atropine can be used to counteract what toxic posioning

A

organophosphates

195
Q

How do you tell difference marasmus and kwashiorkor

A

wkashiorkor still in 60% and up weight

196
Q

exposure to huge amounts of radiation will cause what

A

cerebral syndrome

197
Q

What gene is associated with obesity

A

MC4R

198
Q

in a full thickness burn what component of skin will you have lost completely

A

dermal appendages like hair follicles and sweat glands

199
Q

what is beriberi

A

thiamine deficiency leading to heart failure

200
Q

what is more potent crack or cocaine

A

crack

201
Q

what are greatest threats to burn victims

A

chock sepsis and respiratory insufficiency

202
Q

what type of necrosis occurs with burns

A

coagulative

203
Q

radon exposure can lead to what

A

lung cancers

204
Q

describe liver and small bowel in kwashiorkor vs marasmus

A

the liver is enlarged in kwashiorkor and the small bowel shows decreased mitotic index in the glandular crypts

205
Q

what are the clinical features of a selenium deficiency

A

myopathy and cardiomyopathy

206
Q

besides adiponectin and leptin what else does adipose tissue produce

A

TNF IL6 IL1 and IL18

results in high levels circulating C reactive protein

Patho II (7 decks)

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