Final Exam Flashcards

1
Q

T/F: Carcinogenesis occurs from one or two genetic alterations

A

False: …results from many genetic alterations

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2
Q

What are the 3 classes of extrinsic carcinogenic agents?

A

Chemical
Radiant Energy
Microbial

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3
Q

T/F: Direct acting chemical carcinogens require metabolic conversion first.

A

False: direct acting=no metabolic conversion

indirect acting=requires metabolic conversion

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4
Q

Smoked meat is an example of a direct or indirect acting chemical carcinogen.

A

Indirect

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5
Q

Aflatoxin B1, found on the shell of ___, typically mutates TP53.

A

Peanuts

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6
Q

T/F: Following initiator-promotion sequence, the promoter must follow exposure to chemical mutagen.

A

True

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7
Q

What is irradiation?

A

High energy waves capable of ionizing atoms and having mutagenic effects.

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8
Q

Hiroshima victims would be an example of what type of external carcinogenic agent?

A

Radiation carcinogenesis

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9
Q

What is the most common skin cancer?

A

Basal cell carcinoma

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10
Q

What is the most common form of cancer in the US, (it actually contradicts the statement at the beginning of the packet)?

A

Skin cancer (yes it says prostate & breast in the beginning of the packet..idk)

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11
Q

What is the Human T Cell lymphotropic virus 1 (HTLV-1)?

A

Oncogenic virus spread via bodily fluids increasing likelihood of T Cell lymphoma/leukemia

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12
Q

What gene should you associate HTLV-1 with?

A

TAX gene

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13
Q

What are the 4 oncogenic DNA viruses?

A
  1. HPV
  2. EBV (HHV4)
  3. HBV, HCV (Hep B and C)
  4. Kaposi sarcoma herpesvirus (KSHV or HHV8)
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14
Q

What types of HPV cause relatively benign papillomas?

A

HPV6 and HPV11

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15
Q

What types of HPV cause squamous cell carcinoma?

A

HPV16 and HPV18

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16
Q

T/F: Human papilloma virus is known for activating retinoblastoma (Rb) and decreasing growth.

A

False: Rb DEactivation and INCR growth

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17
Q

What was the first oncovirus discovered?

A

Epstein Barr Virus

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18
Q

Is the EBV more likely to cause T cell or B cell cancers?

A

B Cell cancers like Hodgkin Lymphoma

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19
Q

Which type of cancer are the Hepatitis B and C viruses associated with?

A

Liver CA (hepatocellular carcinoma)

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20
Q

HBV and HCV is still prevalent in which two regions of the world?

A

Africa and SE Asia

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21
Q

Which organism was the 1st “cancer bacteria” discovered and also causes 90% of peptic ulcer disease?

A

Helicobacter pylori

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22
Q

T/F: 90% of Helicobacter pylori infections lead to cancer.

A

False: 3% progress to cancer

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23
Q

Which 3 immune cell types have antitumor effector mechanisms?

A

T Killer cells, NK cells, Macrophages

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24
Q

What is the most common cancer among immunocompromised individuals?

A

B Cell lymphomas

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25
Q

What is “wasting syndrome”?

A

(Cachexia) Unexplained weight loss that is irreversible even with nutrition changes; typically accompanies end stage cancer

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26
Q

What are paraneoplastic syndromes?

A

Features that show up around the time of cancer development

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27
Q

What % of cancer patients exhibit paraneoplastic syndrome?

A

10-15%

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28
Q

List 3 ways of diagnosing cancer

A
  1. Biopsy
  2. Fine-needle aspiration
  3. Cytologic smear
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29
Q

T/F: Tumor markers are non-diagnostic enzymes or hormones that can be used for screening for cancer.

A

True

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30
Q

T/F: The number of genes present correlates to the complexity of the species.

A

False: otherwise a flea would be more complex than us

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31
Q

T/F: All hereditary disorders are congenital but not all congenital disorders are hereditary.

A

True: congenital simply means present at birth

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32
Q

What is a point mutation?

A

a nucleotide base is replaced by another

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33
Q

The insertion/deletion of 1 or 2 nucleotides resulting in an altered reading frame is called a ___ mutation.

A

Frameshift

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34
Q

What does pleiotropy mean?

A

A single mutation having various phenotypic effects, ex: Li Fraumeni Syndrome or Marfan Syndrome

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35
Q

In an autosomal dominant disorder with one parent affected, what is the offsprings chance of disorder manifesting?

A

50% and males/females affected equally

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36
Q

What is reduced penetrance and give an example?

A

They have the mutation but still phenotypically normal; example is BRCA1 and BRCA2 genes

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37
Q

In an autosomal recessive disorder with both parents being carriers, what % of offspring will be affected? Carriers?

A

25% normal
50% carriers
25% affected

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38
Q

How are X-linked recessive disorders passed?

A

By carrier mother, affects 50% of male offspring and 50% of female offspring will be carriers

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39
Q

Genetically, what is Marfan Syndrome?

A

Aut. Dominant syndrome leading to Fibrillin gene mutation

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40
Q

What does pathognomic mean?

A

No single sign is definitive of having a disorder

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41
Q

What disorder likely possesses long limbs, joint hypermobility, chest deformities, and an elongated face?

A

Marfan syndrome

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42
Q

What is pes planovalgus?

A

Flat feet; can be associated with Marfan Syndrome

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43
Q

What structure is defective in individuals with Ehlers-Danlos Syndrome?

A

Defective collagen–> hyperextensible skin and hypermobile joints

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44
Q

Is familial hypercholesterolemia an autosomal dominant or recessive disorder and what does it affect?

A

Autosomal dominant defect of LDL receptor

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45
Q

Which subtype of familial hypercholesterolemia has a childhood onset and is much more severe?

A

Homozygous; (heterozygous is adult onset and less severe)

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46
Q

What are xanthomas and which disease are they characteristic to?

A

Cholesterol deposits on tendons seen in familial hypercholesterolemia

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47
Q

What is the likely cause of death in individuals with Marfan syndrome?

A

Ruptured aorta

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48
Q

T/F: Cystic fibrosis is an autosomal dominant disorder affecting the CFTR gene.

A

False: autosomal recessive

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49
Q

Which disorder would likely show a positive Steinberg sign: Cystic Fibrosis, Ehler-Danlos, or Marfan Syndrome

A

Marfan Syndrome

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50
Q

What is the most lethal genetic disease in Caucasians?

A

Cystic fibrosis

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51
Q

How do people with Cystic Fibrosis usually die?

A

Chronic pulmonary infections

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52
Q

Phenylketonuria is an autosomal ___ disorder resulting in the accumulation of ___.

A

Recessive; phenylalanine

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53
Q

A “salty kiss” may be the first sign a baby may have ___ ___.

A

Cystic Fibrosis

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54
Q

Which genetic disorder can exhibit a musty or mousy odor to their urine/sweat?

A

Phenylketonuria (PKU)

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55
Q

Why do individuals with phenylketonuria exhibit decreased pigmentation that can be confused for albinism?

A

Lack phenylalanine, a precursor for tyrosine (which is a precursor for melanin)

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56
Q

Galactosemia is an autosomal ___ disorder affecting what enzyme?

A

Recessive; GALT

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57
Q

In babies with phenylketonuria, mental disabilities can be avoided if what is restricted and what is supplemented?

A

Restrict phenylalanine since it can’t be broken down…

supplement tyrosine

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58
Q

What should be restricted in individuals with galactosemia?

A

Galactose

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59
Q

Which organ is likely to be enlarged in babies with galactosemia?

A

Liver resulting in outward jaundice

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60
Q

Lysosomal storage diseases lack which enzymes?

A

Lysosomal enzymes (autosomal recessive)

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61
Q

What are the 5 LSD’s?

A
Tay Sach's 
Niemann Pick Types A & B
Niemann Pick Type C
Gaucher 
Mucopolysaccaridosis
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62
Q

The inability to metabolize Gm2 gangliosides is characteristic of which LSD?

A

Tay-Sach’s Dz

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63
Q

Which enzyme is mutated with Tay Sach’s Dz?

A

Hexosaminidase A enzyme

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64
Q

This disease with cherry red central macula is typically fatal by age 2-3.

A

Tay Sach’s Dz

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65
Q

What accumulates in Niemann-Pick Dz Type A&B?

A

Sphingomyelin accumulates –> enlarged spleen and liver

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66
Q

Which is most severe and typically fatal by age 3: Niemann Pick Type A, B or C?

A

N.P Type A

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67
Q

Niemann Pick Type B varies from A in that it shows no ____ damage.

A

Neuronal

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68
Q

Which is the most common and has defective lipid transport: Niemann Pick Type A, B or C?

A

N.P Type C

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69
Q

What 3 things accumulate in Niemann Pick Type C?

A
  1. Cholesterol
  2. Gm1 gangliosides
  3. Gm2 gangliosides
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70
Q

What is mutated in Niemann Pick Type C?

A

NPC1 or NPC2

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71
Q

____ gene is mutated in Gaucher Dz leading to the accumulation of ____.

A

Glucocerebrosidase gene mutated;

Glucocerebrosides accumulate

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72
Q

T/F: Gaucher cells are enlarged liver cells

A

False: enlarged phagocytes but a common symptom of Gauchers is hepatosplenomegaly

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73
Q

What is pancytopenia?

A

reduction in all blood cells resulting in anemia and easy bruising (associated with Gaucher’s Dz)

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74
Q

99% of individuals with Gauchers have the Type__ which is less severe with no neuro disturbances.

A

Type 1

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75
Q

T/F: Wrinkled tissue paper cytoplasm and Erlenmeyer’s flask deformity are characteristic of Gaucher Dz.

A

True

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76
Q

What 2 LSD’s are Ashkenazi Jews particularly vulnerable to?

A
  1. Tay Sach’s Dz

2. Gaucher’s Dz

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77
Q

What is mucopolysaccharidosis?

A

Group of disorders regarding deficiency in ECM breakdown enzymes

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78
Q

What are the two types of mucopolysaccharidosis’?

A
Type 1 (Hurler)
Type 2 (Hunter)
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79
Q

Alpha-L-iduronidase deficiency=____ Syndrome

L-iduronate sulfatase deficiency= ____ Syndrome

A

Alpha…=Hurler

L-idur….=Hunter

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80
Q

Which syndrome is X-Linked: Hurler or Hunter?

A

Hunter

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81
Q

Which syndrome is lethal by 6-10 years: Hurler or Hunter?

A

Hurler, Hunters is more mild

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82
Q

Which syndrome accumulates heparin sulfate and dermatan sulfate: Hurler or Hunter?

A

Both!

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83
Q

What is the shorter name for glycogen storage diseases?

A

Glycogenoses

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84
Q

Which autosomal recessive disorder involves abnormal glycogen metabolism?

A

Glycogenoses

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85
Q

Match the following:
von Gierke Dz muscle phosphorylase
McArdle Dz glucose 6 phosphatase
Pompe Dz lysosomal acid maltase

A

von Gierke-glu6phosphatase
McArdle-muscle phosphorylase
Pompe-lysosomal acid maltase

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86
Q

Which glycogen storage disease results in muscle weakness and cramps, and myoglobinurea?

A

McArdles Dz

87
Q

Which lysosomal storage disease is lethal by age 2?

A

Pompe: note that it’s technically a LSD not a GSD

88
Q

Which GSD results in hepatomegaly and hypoglycemia?

A

von Gierke

89
Q

What causes 50% of spontaneous first tri abortions?

A

Cytogenic disorders

90
Q

T/F: In general a loss of genetic material is more severe than a gain of genetic material.

A

True

91
Q

What is Trisomy 18: Down, Edwards, Patau, or Cri du chat Syndrome?

A

18-Edwards

92
Q

Which chromosome is fragmented in Cri du Chat Syndrome?

A

5th Chromosome

93
Q

Which trisomy is lethal by 1 year old 80% of the time?

A

Trisomy 13- Patau Syndrome

94
Q

T/F: Down Syndrome is the most common of the trisomies.

A

True

95
Q

What is the relationship between maternal age and Trisomy 21 incidence?

A

The older the mother, the increased incidence

96
Q

Up to 30% of Down Syndrome have ___ ___ instability.

A

Atlanto-axial

97
Q

DiGeorge Syndrome and Velocardiofacial Syndrome are associated with the deletion of what?

A

Deletion of band 11 on chromosome 22 (22q11.2)

98
Q

Which cytogenic disorder involves simian creases, epicanthic folds, and a flat facial profile?

A

Trisomy 21/Down Syndrome

99
Q

DiGeorge Syndrome has a decrease in which immune cell immunity?

A

T-Cell immunity

100
Q

____ Syndrome appears male whereas ___ Syndrome appears female.

A

Klinefelter=male

Turner=female

101
Q

T/F: Klinefelter Syndrome involves and extra X on a male resulting in hypogonadism and sterility.

A

True

102
Q

What are the 2 risks associated with Klinefelter Syndrome?

A

Incr maternal age, irradiation

103
Q

An absence of 1 X chromosome resulting in short stature, amenorrhea, and neck webbing is associated with ____ Syndrome.

A

Turner Syndrome

104
Q

T/F: Fragile X Syndrome affects primarily females.

A

False: males

105
Q

T/F: 20% of males affected with Fragile X are phenotypically normal.

A

True

106
Q

T/F: An example of mitochondrial gene mutation disorder is Leber hereditary optic neuropathy.

A

True

107
Q

In a mitochondrial gene mutation an affected mom will have ___ affected children and an affected dad will have ___ affected children.

A

mom–>all affected kids

dad–>no affected kids

108
Q

What is Angelman’s syndrome, genetically speaking?

A

Paternal imprinting

Maternal deletion of 15q12

109
Q

What is the syndrome with maternal imprinting and paternal deletion of 15q12?

A

Prader Willi Syndrome

110
Q

T/F: Prader Willi Syndrome involves ataxia and inappropriate laughter.

A

False: Angelmans Syndrome

111
Q

What is the MC cause of death in kids under 1 yr of age?

A

Congenital malformation or chromosomal abnormality

112
Q

Between 1-4 yrs old, where does congenital malformation/chromosomal abnormality fall on list of leading cause of death?

A

2nd to Accidents

113
Q

What are the 2 methods of perinatal infections?

A

Transcervical/ascending

Transplacental/descending

114
Q

What is TORCH?

A

Pathogens known for causing dz by crossing the placenta. (Toxoplasma, Other, Rubella virus, CMV, Herpes Simplex Virus)

115
Q

T/F: It’s more common for bacteria to infect transcervically than for viruses.

A

True

116
Q

What is considered “premature”?

A

Less than 37 weeks gestation

117
Q

Type II pneumocytes produce surfactant, which is decreased in ___ ____ Syndrome.

A

Respiratory Distress Syndrome

118
Q

T/F: 60% of infants born under 28 weeks gestation have RDS.

A

True

119
Q

What is atelectasis?

A

Difficulty in inflating alveoli due to decreased surfactant production in RDS

120
Q

Where is necrotizing enterocolitis most common?

A

Cecum, ileum, and ascending colon

121
Q

When is SIDS most common?

A

Between the ages of 2-4 months

122
Q

What is the 2nd most common cause of death in infants under 1 yr? 3rd most common?

A

Low birth weight=2nd

SIDS=3rd

123
Q

What are 4 risk factors associated with SIDS?

A
  1. Prone sleeping
  2. Soft bedding
  3. Bed Co Sharing
  4. Thermal stress
124
Q

What is the triple risk model and what disease is it associated with?

A

3 risks associated with SIDS, 1. vulnerable infant 2. critical development period 3. exogenous stressor

125
Q

T/F: Hydrops fetalis and cystic hygroma are both lethal to infants.

A

False: cystic hygroma may not be lethal

126
Q

What is fetal hydrops?

A

Accumulation of severe edema likely due to chromosomal abnormalities, (but may be due to antibody induced hemolysis)

127
Q

What are the 3 benign pediatric tumors?

A

Hemangioma
Lymphangioma
Sacrococcygeal teratomas

128
Q

Which benign pediatric tumor usually self resolves by age 7?

A

Hemangioma

129
Q

What is the most common germ cell tumor of childhood?

A

Sacrococcygeal teratomas

130
Q

T/F: Sacrococcygeal teratomas are likely benign and external.

A

True

131
Q

T/F: Spontaneous regression is more likely in pediatric malignant tumors.

A

True

132
Q

Neuroblastomas are benign or malignant?

A

malignant

133
Q

Homer-Wright pseudo-rosettes are associated with ___- but Flexner-Wintersteiner rosettes are associated with ____.

A

Pseudo-rosettes=neuroblastoma

Rosettes=retinoblastoma

134
Q

What is a Homer-Wright pseudo-rosette?

A

Neutrophil surrounded by tumor cells, likely secreting catecholamines like NE

135
Q

T/F: “Blueberry muffin baby” is characteristic of retinoblastoma.

A

False: blueberry muffin baby-neuroblastoma

136
Q

What are the common sites of mets for neuroblastoma?

A

Liver, lungs, and bone marrow

137
Q

What is the most common pediatric eye malignancy?

A

Retinoblastoma

138
Q

Is sporadic or genetic retinoblastoma more common?

A

Sporadic 60%

Genetic 40%

139
Q

What are Flexner-Wintersteiner rosettes?

A

Cuboidal cells surrounding empty lumen

140
Q

T/F: Wilm’s Tumor, or nephroblastoma, is a malignant pediatric kidney tumor commonly affecting 2-5 year olds.

A

True

141
Q

T/F: Less than 1% of chemicals used in the US have been tested for health impact

A

True

142
Q

What does xenobiotic mean?

A

Chemicals not produced or expected in an organism but still found inside it

143
Q

What organ is most vulnerable to environmental pollution?

A

Lungs

144
Q

Which colorless, odorless gas is the result of incomplete oxidation of fossil fuels?

A

Carbon Monoxide

145
Q

Which type of poisoning is the result of occupational fumes of carbon monoxide: acute or chronic?

A

Chronic

146
Q

Which type of outdoor air pollution results in cherry red skin and mucus membranes?

A

Acute Carbon Monoxide poisoning

147
Q

T/F: Hemoglobin has a higher affinity for oxygen than carbon monoxide making life possible.

A

False: Hemoglobin has 200x affinity for CO than O2

148
Q

What is the most common indoor pollutant?

A

Tobacco smoke

149
Q

____ are airborne particles that contain or were from living organisms.

A

Bioaerosols

150
Q

Which colorless, odorless gas occurs naturally from the uranium decay in the soil?

A

Radon

151
Q

Radon increases the risk for what type of cancer?

A

Lung cancer

152
Q

Do adults or children have higher lead absorption with irreversible damage?

A

Children

153
Q

What types of fish have the highest levels of mercury?

A

Largest, oldest, carnivorous fish

154
Q

T/F: There has been no association with thimerosal and autism spectrum disorder.

A

True

155
Q

Which environmental pollutant occurs naturally in the soil and increases the risk for skin and lung cancer?

A

Arsenic

156
Q

What 3 areas of the body does cadmium damage primarily?

A

Lungs, kidneys, bone

157
Q

What is Itai-itai disease?

A

Bone loss and renal failure associated with cadmium pollution

158
Q

What is a “pack year”?

A

(Packs smoked per day) x (years smoked)

to calculate tobacco exposure

159
Q

What % of lung cancer diagnoses are smokers?

A

90%

160
Q

T/F: Alcohol is absorbed unaltered in the stomach and SI then metabolized in liver.

A

True

161
Q

50% of Asians have a defective from of ____ ___ causing tachycardia, tachypnea, and flushing.

A

acetaldehyde dehydrogenase

162
Q

Chronic alcoholism can cause thiamine (B1) deficiency leading to ____ Syndrome.

A

Korsakoff Syndrome

163
Q

T/F: Fetal Alcohol Syndrome results in CNS damage, megalocephaly, and spontaneous abortion.

A

False: CNS damage, microcephaly and facial malformation

164
Q

T/F: Oral contraceptives can protect against endometrial and ovarian cancers.

A

True

165
Q

Which therapeutic drug can cause jaundice and accidental overdose due to its relatively low toxic dose?

A

Acetaminophen

166
Q

What is the clinical abbreviation for acetaminophen?

A

APAP

167
Q

T/F: ASP is the clinical abbreviation for aspirin.

A

False: Aspirin is ASA

168
Q

T/F: Aspirin is a more effective antipyretic than acetaminophen

A

True

169
Q

T/F: Cocaine toxicity is related to it’s purity, not the dose.

A

True

170
Q

Is cocaine addictive?

A

Psychologically yes

171
Q

Which recreational drug is an opioid derived from the poppy plant?

A

Heroin

172
Q

What side of the heart is most affected by heroin use?

A

Right side (and lungs) b/c injected intravenously

173
Q

What is the MC used illicit drug?

A

Marijuana

174
Q

T/F: A thermal injury is a heat related injury

A

False: It can be excessive heat or cold

175
Q

What are the two important parts of treating burn victims?

A
  1. Replace fluids and electrolytes

2. Manage infections

176
Q

Hypovolemic shock results when burns cover over __% of the body surface.

A

20%

177
Q

What is the most common pathogen associated with burn victims?

A

Pseudomonas aeruginosa

178
Q

What is the key characteristic regarding heat stroke?

A

Loss of thermoregulation so victim won’t be sweating

179
Q

What are the MC sources of irradiation?

A

X rays and Gamma rays

180
Q

How much exposure to irradiation is man-made?

A

20%, the rest is from the environment

181
Q

Which types of cells are more sensitive to irradiation?

A

Labile cells like gonads, bone marrow, lymph tissue, and GI cells

182
Q

T/F: Mature RBC’s are radioresistant resulting in anemia 2-3 weeks after exposure.

A

True

183
Q

When you are missing 1 or more nutrients, it is called ___ malnutrition; whereas if you have adequate intake but some storage/utilization issue it’s called ___malnutrition.

A

Primary; Secondary

184
Q

Which nutritional diseases result from an inadequete protein intake?

A

Protein energy malnutrition (Marasmus, Kwashiorkor)

185
Q

Which nutritional disease results from decr protein leading to edema, visceral protein breakdown and anorexia?

A

Kwashiorkor

186
Q

Which nutritional disease results from decr protein due to overall decr in calories?

A

Marasmus

187
Q

What is being broken down in Marasmus?

A

Skeletal muscle

188
Q

T/F: Marasmus victims experience decreased B cell immunity and an enlarged head.

A

False: decr in T cell imunity and no enlarged head (just looks large compared to emaciated thorax)

189
Q

People with ___ ____ may experience amenorrhea, lanugo, and cold intolerance.

A

Anorexia Nervosa

190
Q

What is more common: anorexia nervosa or bulimia?

A

Bulimia

191
Q

___ ____ is the esophageal irritation associated with bulimia.

A

Barrett esophagus

192
Q

What are the four fat soluble vitamins?

A

A, D, E, K

193
Q

T/F: The liver can store a 6 month supplyof vitamin D.

A

False: vitamin A

194
Q

Vitamin __ maintains vision by maintaining rods and cones.

A

A

195
Q

What is a common problem resulting from vitamin A deficiency?

A

Night blindness (rhodopsin)

196
Q

Vitamin D maintains plasma calcium and what?

A

Phosphorus

197
Q

The active form of vitamin D is what type of hormone?

A

Steroid hormone

198
Q

What regions are prone to vitamin D deficiency?

A

Northern regions or other areas lacking UV light exposure

199
Q

Vitamin D deficiency in kids is called ____, and ___ in adults.

A

Rickets; osteopenia

200
Q

Is it possible to reach toxic doses of vitamin D?

A

By oral doses yes…not by sunlight exposure

201
Q

What does a deficiency in vitamin C lead to?

A

Scurvy

202
Q

Bleeding gums, joint issues, and decreased healing are all signs of vitamin C deficiency resulting in impaired ___ formation.

A

Collagen

203
Q

Is mega-dosing with vitamin C a bad thing?

A

No, most is excreted in urine however hyperuricosuria may ensue

204
Q

T/F: Increasing uptake in vitamin C can protect against the common cold and may reduce the risk of cancer.

A

False: no significant evidence to support either statement

205
Q

A BMI of 18.5-25 is ___, a BMI between __ and __ is overweight, and a BMI greater than __ is considered obese.

A

Normal; 25-30; 30

206
Q

What percentage of Americans are obese?

A

34%; roughly 2/3 are considered overweight

207
Q

T/F: Men are more likely to have the ‘apple’ shape and women are more likely to have the ‘pear’ shape.

A

True

208
Q

What is the LEP gene and who has more of it?

A

codes for leptin; increased in people w/ more adipose

209
Q

__ decreases your appetite, whereas ___ increases your appetite.

A

Leptin; ghrelin

210
Q

T/F: Theoretically, people who carry more fat should have a decreased appetite.

A

True; fat releases leptin which is the appetite suppressor

211
Q

What is the correlation between obesity and hypertension?

A

More obese, the greater the hypertension

212
Q

If you restrict ___ from your diet, it can help reduce hypertension.

A

sodium

213
Q

T/F: Restricting calories can lead to a longer lifespan.

A

True

214
Q

T/F: An increase in animal fats in your diet along with lower amounts of fiber has been linked to renal cancer.

A

False…colorectal cancer