Exam II Flashcards
(539 cards)
1
Q
any swelling, nodule or protuberance
A
tumor
2
Q
abnormal uncontrolled growth of cells
A
neoplasia
3
Q
neoplasias are identified by
A
clonal genetic mutations
4
Q
describe clonal genetic mutations
A
entire parenchyma of neoplasm arises from one genetically altered cell
5
Q
neoplasms that have acquired mutations that allow for invasion and metastatic potential
A
malignant neoplasm
6
Q
two basic components of neoplasms
A
parenchyma
stroma
7
Q
dense, rock-hard fibrotic stroma of a neoplasm describes…
A
scirrhous desmoplastic reaction
8
Q
epithelial malignant neoplasm
A
carcinoma
9
Q
mesenchymal malignant neoplasm
A
sarcoma
10
Q
mass producing malignancy formed by lymphoid cells
A
lymphoma
11
Q
non-mass producing malignancy of hematopoietic cells
A
leukemia
12
Q
combined mesenchymal and epithelial malignancy
A
carcinosarcoma
13
Q
melanocytic malignant neoplasm
A
melanoma
14
Q
tumor composed of very immature undifferentiated cells
A
blastoma
15
Q
name the benign and malignant neoplasms:
blood vessels
A
hemangioma
angiosarcoma
16
Q
name the benign and malignant neoplasms:
lymph vessels
A
lymphangioma
lymphangiosarcoma
17
Q
name the benign and malignant neoplasms:
mesothelium
A
benign fibrous tumor
mesothelioma
18
Q
name the benign and malignant neoplasms:
brain coverings
A
meningioma
invasive meningioma
19
Q
name the malignant neoplasms:
hematopoetic cells
A
leukemias
20
Q
name the malignant neoplasms:
lymphoid tissue
A
leukemias and lymphomas
21
Q
name the benign and malignant neoplasms:
smooth muscle
A
leiomyoma
leiomyosarcoma
22
Q
name the benign and malignant neoplasms:
striated muscle
A
rhabdomyoma
rhabdomyosarcoma
23
Q
name the name the benign and malignant epithelial neoplasms:
liver cells
A
hepatic adenoma
hepatocellular carcinoma (hepatoma)
24
Q
name the name the benign and malignant epithelial neoplasms:
placental epithelium
A
hydatidiform mole
choriocarcinoma
25
name the name the benign and malignant epithelial neoplasms:
tumor of melanocytes
melaoncytic nevus
malignant melanoma
26
malignant neoplasm from cells that make sperm
seminoma
27
neoplasms with more than one neoplastic cell type derived from ONE germ cell layer
mixed tumors
28
benign mixed tumor of salivary gland
pleomorphic adenoma
29
malignant mixed tumor of renal anlage
Wilms tumor (nephroblastoma)
30
neoplasm with more than one neoplastic cell type derived from MORE THAN ONE germ cell layer
teratogenous
31
what germ layer do gut and lung epithelium arise from?
endoderm
32
what germ layer do skin and parathyroid glands epithelium arise from?
ectoderm
33
what germ layer do fat and renal epithelial tubules arise from?
mesoderm
34
what germ layer do brain and nervous tissues arise from?
ectoderm
35
what germ layer do glands, including liver and pancreas, arise from?
endoderm
36
what germ layer do bones and cartilage arise from?
mesoderm
37
mature teratoma:
benign/malignant?
AKA?
benign
dermoid cyst
38
mature teratoma that contains a single tissue type
monodermal teratoma
39
mature teratoma found in the ovary that contains ONLY thyroid follicles
struma ovarii
40
immature teratoma:
malignant or benign?
malignant
41
teratoma containing carcinoma, sarcoma, and/or germ cell malignancy
malignant teratoma
42
benign non-neoplastic tumor-like malformation resulting from faulty development in an organ and composed of abnormally arranged tissue elements normally seen in that organ
hamartoma
43
congenital heterotopic rest of cells (NOT a neoplasm) -- normal tissue in abnormal location
choristoma
44
decreased differentiation--does NOT look like mature tissue of origin
anaplasia
45
variation in appearance of cells within the tumor
pleomorphism
46
extra DNA
nuclear enlargement
47
marked increase in content per nucleus with more intense blue staining by hematoxylin
nuclear hyperchomicity
48
higher rate of growth seen in malignancy is caused by what?
increased mitotic activity d/t loss of normal cell cycle control
49
increased fibrous tissue surrounding invading parenchymal cells
desmoplasia
50
dense fibrous desmoplastic reaction making cancer HARD to palpation
scirrhous
51
increased blood vessels
angiogenesis
52
new foci of neoplastic growth away from the initial neoplastic mass
metastasis
53
is anaplasia (lack of/dedifferentiation) indicative of neoplasia?
almost always!
54
what are 4 characteristics of cellular anaplasia
pleomorphism
abnormal nuclear morphology
increased mitotic activity
loss of polarity
55
pleomorphism may or may not be ______
malignant!
56
full thickness epithelial dysplasia with no evidence of tissue invasion by the abnormal cells
carcinoma in situ
57
HPV cytopathic changes are called
Koilocytototic atypia
58
extreme full thickness dysplasia with no invasion
carcinoma in situ
59
are malignant tumors encapsulated?
No!
60
____ unequivocally marks a tumor as malignant
metastasis
61
what are sentinel lymph nodes
nodes that the tumor spreads to first
62
what is significant about the hematogenous spread from hepatic, renal and adrenocortical areas?
can propagate in veins--can grown as a mass into the heart
63
cancer metastases from which areas can propagate in veins up to the heart
hepatic
renal
adrenocortical
64
venous connections that extend from pelvis to skull along the vertebral column
Batson (paravertebral) veins/plexus
65
what is classic route of metastasis for prostatic cancer (and renal, breast, rectal, and bladder)
Batson veins/plexus
66
what cancers metastasize via Batson veins/plexus
prostatic!
also renal, breast, rectal, bladder
67
probability of being dx with a disease during a given period of time
incidence
68
number of new cases of a disease per number of people at risk
incidence
69
total number of cases of diseases existing in a population
prevalence
70
number of deaths divided by total population
mortality rate
71
what is the most common cancer INCIDENCE in males vs. females
males: prostate
females: breast
72
what is the most common cancer deaths in males vs. females
lung, bronchus cancer for BOTH!
73
HTLV-1 (oncogenic RNA virus)
adult T-cell leukemia/lymphoma
74
HCV (oncogenic RNA virus)
hepatocellular carcinoma
75
HBV (oncogenic DNA virus)
hepatocellular carcinoma
76
HPV (oncogenic DNA virus)
types? cancer?
types 16 and 18!!
carcinomas of cervix, anus, penis, oropharynx
77
HHV-8 (oncogenic DNA virus)
Kaposi sarcoma and primary effusion lymphoma
78
EBV (oncogenic DNA virus)
Burkitt lymphoma
Hodgkin lymphoma
nasopharyngeal carcinoma
79
aspergillus (fungus)
toxin? cancer?
aflatoxin B1
hepatocellular carcinoma (p53 mutation)
80
Schistosoma haematobium (parasite)
bladder cancer
81
helicobacter pylori (bacteria)
MALT lymphoma and gastric adenocarcinoma
82
chronic exposure to soot in chimney sweeps can result in...
scrotal skin cancer (NOT TESTICULAR CA!)
83
change in incidence of various cancers with migration from Japan to US provides evidence that cancers are related to ____
environmental factors
84
anticancer drugs may cause cancers! especially ____
leukemias
85
vinyl chloride
cancer? which pts?
vascular CA in liver
workers in a factory making PVC pipes
86
polyvinyl chloride
cancer? where's it found?
NOT associated with cancer
found in PVC pipes
87
arsenic and arsenic compounds
skin carcinomas
88
asbestos
cancers?
found where?
lung, esophageal, gastric, and colon carcinoma, mesothelioma
construction, brake linings, floor tiles
89
benzene
cancers?
acute myeloid leukemia
90
radon
cancers?
found where?
lung carcinoma
from decay of minerals containing uranium--quarries and underground mines
91
vinyl chloride
cancers?
found where?
hepatic angiosarcoma
monomer for vinyl polymers (PVC industry)
92
associated neoplasm and etiologic agent?
asbestosis
lung carcinoma, mesothelioma
asbestos fibers
93
associated neoplasm?
inflammatory bowel disease
colorectal cancer
94
associated neoplasm?
lichen sclerosus et atrophicus
vulvar squamous cell carcinoma
95
associated neoplasm and etiologic agent?
chronic pancreatitis
pancreatic carcinoma
alcoholism
96
associated neoplasm and etiologic agent?
chronic or recurrent bronchitis
lung carcinoma
asbestos, smoking
97
associated neoplasm and etiologic agent?
reflux esophagitis with/without Barrett esophagus
esophageal carcinoma
gastric acids
98
associated neoplasm?
Sjogren syndrome, Hashimotos
MALT lymphoma
99
associated neoplasm and etiologic agent?
Opisthorchis, cholangitis
cholangiocarcinioma
liver flukes (opisthorchis viverrini)
100
associated neoplasm and etiologic agent?
gastritis and gastric ulcers
gastric adenocarcinoma, MALT
Helicobacter pylori
101
associated neoplasm and etiologic agent?
hepatitis
hepatocelluar carcinoma
Hepatitis B and or C
102
associated neoplasm and etiologic agent?
osteomyelitis or skin fistula
carcinoma in draining sinuses
bacterial infection
103
associated neoplasm and etiologic agent?
chronic cervicitis
cervical carcinoma
HPV
104
associated neoplasm and etiologic agent?
chronic cystitis
bladder carcinoma
Schistosoma haematobium
105
____ doublings of a single cancer cell leads to 10^__ cells = __ grams of tumor
30
10^9
1 gram
106
what is the minimal size of a tumor for clinical detection
1 gram
107
ERBB1 (EGFR)
mode of activation:
associated human tumor:
mutation
adenocarcinoma of lung
108
ERRB2 (HER)
mode of activation:
associated human tumor:
amplification
breast carcinoma
109
RET
mode of activation:
associated human tumor:
point mutation
multiple endocrine neoplasia 2A and B
110
KIT
associated human tumor:
gastrointestinal stromal tumors
111
ALK
associated human tumor:
adenocarcinoma of lung
112
KRAS
associated human tumor:
colon, lung, pancreatic tumors
113
NRAS
associated human tumor:
melanomas, hematologic malignancies
114
GNAS
associated human tumor:
pituitary adenoma, other endocrine tumors
115
ABL
associated human tumor:
chronic myeloid leukemia
acute lymphoblastic leukemia
116
BRAF
associated human tumor:
melanomas
117
NOTCH1
associated human tumor:
leukemias, lymphomas, breast carcinoma
118
JAK2
associated human tumor:
myeloproliferative disorders
119
C-MYC
associated human tumor:
Burkitt lymphoma
120
N-MYC
associated human tumor:
neuroblastoma
121
CCND1 (Cyclin D)
associated human tumor:
Mantle cell lymphoma
122
oncogenes created by translocation:
Chronic Myelogenous Leukemia
translocation:
affected genes:
(9;22)(q34;q11)
ABL 9q34 / BCR 22q11
123
oncogenes created by translocation:
Burkitt Lymphoma
translocation:
affected genes:
(8;14)(q24;q32)
c-MYC 8q24 / IGH14q32
124
oncogenes created by translocation:
Ewing Sarcoma
translocation:
affected genes:
(11;22)(q24;q12)
FLI 11q24 / EWSR1 22q12
125
___ genes control development of fetus but can also lead to malignancies
PAX genes
126
function of p16/INK4a
binds to cyclin D-CDK4 and promotes the inhibitory effects of RB
127
function of p14/ARF
increases p53 levels by inhibiting MDM2 activity
128
function of RB
tumor suppressor-- prevents G1/S transition
129
function of p53
tumor suppressor induced by DNA damage-- causes cell cycle arrest and apoptosis
130
describe the 2 hit theory
Hit 1 is an inherited mutated gene
Hit 2 is a spontaneous somatic mutated gene
131
what is an example of a 2 hit theory familial cancer?
RB gene in retinoblastoma
132
what is the inherited predisposition to cancer?
APC
familial adenomatous polyposis/colon cancer
133
what is the inherited predisposition to cancer?
NF1, NF2
neurofibromatosis 1 and 2
134
what is the inherited predisposition to cancer?
PTCH
nevoid basal cell carcinoma syndrome
135
what is the inherited predisposition to cancer?
PTEN
Cowden Syndrome
136
symptoms of Cowden syndrome
skin, GI, and CNS hamarthomatous growths
breast, endometrial, and thyroid carcinomas
137
what is the inherited predisposition to cancer?
RB
retinoblastoma, osteosarcoma
138
what is the inherited predisposition to cancer?
VHL
renal cell carcinomas
139
what is the inherited predisposition to cancer?
CDH1
E-cadherin mutation in hereditary diffuse (familial) gastric cancer
140
what is the inherited predisposition to cancer?
Tp53
Li-Fraumeni syndrome
141
what is the inherited predisposition to cancer?
MSH2, MLH1, MSH6
hereditary nonpolyposis colorectal carcinoma (Lynch) Syndrome
142
what is the inherited predisposition to cancer?
BRCA1, BRCA2
breast, ovarian tumors
143
what is the inherited predisposition to cancer?
MEN1, RET
multiple endocrine neoplasia types 1 and 2
144
what is the inherited predisposition to cancer?
APC
familial adenomatous polyposis
145
what is the inherited predisposition to cancer?
PTCH
Gorlin Syndrome = nevoid basal cell carcinoma
146
what is the inherited familial syndrome and predisposition to cancer?
CDH1 (E-cadherin)
hereditary diffuse (familial) gastric cancer
gastric carcinoma, lobular breast carcinoma
147
what is the inherited familial syndrome and predisposition to cancer?
TP53 (p53 protien)
Li-Fraumeni Syndrome
most human cancers
148
what is the inherited familial syndrome and predisposition to cancer?
MSH2, MLH1, MSH6
hereditary nonpolyposis colorectal carcinoma (Lynch) Syndrome
colonic and endometrial carcinoma
149
what is the inherited predisposition to cancer?
WT1
Wilm's tumor
150
what is the inherited familiar syndrome and predisposition to cancer?
MEN1
3 Ps: pituitary, parathyroid, and pancreatic endocrine tumors
151
condition that causes multiple hamartomas (usually skin and thyroid gland) d/t loss of PTEN tumor suppressor function
Cowden Syndrome
152
2 hit condition characterized by DNA mismatch repair abnormality leading to microsatellite instability
Hereditary nonpolyposis colorectal cancer (Lynch Syndrome)
153
MEN1 mutation causes what
Wermer Syndrome
154
Wermer Syndrome (MEN1 mutation) causes what three things?
pancreatic tumors
pituitary adenoma
parathyroid hyperplasia
155
MEN 2A mutation causes what
Sipple Syndrome
156
Sipple Syndrome causes what three things?
parathyroid hyperplasia
Medullary thyroid carcinoma
pheochromocytoma
157
MEN 2B mutation causes what 4 things?
medullary thyroid carcinoma
pheochromocytoma
Marfanoid body habitus
mucosal neuromas
158
FMTC mutation causes what 1 thing?
medullary thyroid carcinoma
159
describe the Warburg Effect
cancer cells tend to convert most glucose to lactate regardless of whether oxygen is present
160
mutation in genes encoding a variety of proteins involved in nucleotide excision repair of cross-linked pyrimidine dimers
xeroderma pigmentosa
161
ATM gene defect; involved in DNA repair; causes neurodegeneration with difficulty coordinating movements
ataxia telangiectasia
162
loss of function of helicase involved in DNA repair leading to short stature, sun-sensitivity, increased risk of cancer
Bloom Syndrome
163
abnormality in genes encoding DNA repair; associated with aplastic anemia, hypopigmentation, skeletal problems, and acute myeloid leukemia
Fanconi anemia
164
progressive loss of body fat and lean body mass accompanied by profound weakness, anorexia, and anemia
cancer cachexia
165
marasmus-like protein energy malnutrition seen with cancer
cancer cachexia
166
complex of symptoms that cannot be explained by spread of the tumor or hormones indigenous to the tumor tissue
paraneoplastic syndrome
167
paraneoplastic syndrome symptoms are from... (2)
products produced by cancer cells (hormones)
immune reaction of the body to the tumor cells
168
paraneoplastic syndromes:
Cushing Syndrome
underlying cancer:
mechanism:
small cell lung carcinoma
ACTH
169
paraneoplastic syndromes:
SIADH
underlying cancer:
mechanism:
small cell lung carcinoma
inappropriately secreted ADH
170
paraneoplastic syndromes:
hypercalcemia
underlying cancer:
mechanism:
squamous cell lung carcinoma
parathyroid hormone-related protein (PTHRP), TGF alpha, TNF, IL-1
171
paraneoplastic syndromes:
polycythemia
underlying cancer:
mechanism:
gastric carcinoma, renal carcinoma
erythropoietin
172
paraneoplastic syndromes:
Carcinoid Syndrome
underlying cancer:
mechanism:
hepatocellular carcinoma, bronchial adenoma, pancreatic carcinoma
serotonin, bradykinin
173
paraneoplastic syndromes:
Myasthenia
underlying cancer:
mechanism:
thymic neoplasms
immunological
174
paraneoplastic syndromes:
Acanthosis nigricans
underlying cancer:
mechanism:
gastric, lung, and uterine carcinoma
secretion of epidermal growth factor
175
paraneoplastic syndromes:
dermatomyositis
underlying cancer:
mechanism:
bronchogenic, breast carcinoma
immunological
176
paraneoplastic syndromes:
venous thrombosis (Trousseau phenomenon)
underlying cancer:
mechanism:
pancreatic carcinoma
tumor products (mucins that activate clotting)
177
paraneoplastic syndromes:
DIC
underlying cancer:
mechanism:
acute promyelocytic leukemia, prostatic carcinoma
tumor products that activate clotting
178
paraneoplastic syndromes:
Nonbacterial Thrombotic Endocarditis
underlying cancer:
mechanism:
advanced cancers
hypercoagulability
179
what is the most important prognostic indicator?
stage
180
grading neoplasms based on tissue differentiation (anaplasia)
histologic grade
181
grading neoplasms based on nuclear pleomorphism (bizarreness)
nuclear grade
182
tumor markers:
human chorionic gonadotropin
trophoblastic tumors, nonseminomatous testicular tumors
183
tumor markers:
calcitonin
medullary carcinoma of thyroid
184
tumor markers:
catecholamine and metabolites
pheochromocytoma
185
tumor markers:
ectopic hormones
paraneoplastic syndromes
186
tumor markers:
alpha fetoprotein
liver cell cancer, nonseminomatous germ cell tumors of testis
187
tumor markers:
carcinoembryonic antigen
carcinomas of the colon, pancreas, lung, stomach, and heart
188
tumor markers:
prostatic acid phosphatase
prostate cancer
189
tumor markers:
neuron-specific enolase
small-cell cancer of lung, neuroblastoma
190
tumor markers:
prostate-specific antigen and membrane antigen
prostate cancer
191
tumor markers:
CA-125
ovarian cancer
192
tumor markers:
CA-19-9
colon cancer, pancreatic cancer
193
tumor markers:
CA-15-3
breast cancer
194
haploid is ___ chromosomes
23
195
diploid is ___ chromosomes
46
196
cells that contain an extra or are missing a chromosome are termed
aneuploid
197
monosomy
only 1 copy of a chromosome
198
trisomy
3 copies of a chromosome
199
aneuploidy results from... during...
nondisjuction during meiosis (anaphase I or II)
200
Trisomy 21
Down Syndrome
201
Down syndrome karyotype
47, XX(or XY), +21
202
Trisomy 18
Edwards syndrome
203
cardiac defects, rocker feet, and poor prognosis (few survive first year) describes what syndrome
Edwards Syndrome (Trisomy 18)
204
Trisomy 18 more frequently results from nondisjunction during
meiosis II
205
Edwards Syndrome karyotype
47, XX (or XY), +18
206
Trisomy 13
Patau Syndrome
207
holoprosencephaly, cleft lip, and cardiac defects with a worse prognosis than Edwards describes
Patau Syndrome
208
Patau Syndrome karyotype
47, XX (or XY), +13
209
Monosomy of X chromosome
Turner Syndrome
210
short stature, gonadal dysgenesis, edema of foot at birth, and shortened 4th metacarpal describes what
Turner Syndrome
211
Turner syndrome karyotype
45, X
212
biologically male, macrocephaly, macroorchidism, and hypertelorism (wide set eyes) with risks of behavior disorders
47, XYY Syndrome
213
47, XXY
Klinefelter Syndrome
214
most frequent aneuploidy of sex chromosomes
Klinefelter (47, XXY)
215
hypogonadism, low testosterone, underdeveloped secondary sex characteristics, gynecomastia (breast development), and infertility describe what
Klinefelter Syndrome (47, XXY)
216
breakage of 2 nonhomologous chromosomes with exchange of broken fragment
reciprocal translocation
217
describe the Philedelphia chromosome
balanced translocation between ABL on chromosome 9 and BCR on chromosome 22 that leads to constitutively active BCR-ABL tyrosine kinase --> chronic myelogenous leukemia
218
parents with a balanced translocation can yield ____ in offspring
unbalanced translocation
219
what involves 2 acrocentric chromosomes that fuse at the centromere
Robertsonian translocation
220
Robertsonian translocation results in loss of
short arm
221
5% of Down Syndrome cases are caused by inheriting the derivative chromosome from a
Robertsonian translocation
222
loss of chromosome fragment at the end of a chromosome
terminal deletion
223
loss of chromosome fragment at the center portion of arm
interstitial deletion
224
small chromosomal deletions not detectable with banding
microdeletions
225
deletion 5p
Cri-du-Chat Syndrome
226
what causes a laryngeal defect leading to cat-like, high-pitched cries?
Cri-du-Chat Syndrome (deletion 5p)
227
deletion at 4p16
Wolf-Hirschhorn Syndrome
228
Wolf-Hirschhorn Syndrome is a deletion at
4p16
229
what condition causes failure to thrive, ID, strong socialization skills with weak verbal skills
Wolf-Hirschhorn Syndrome
230
22q11 deletion
DiGeorge Syndrome
231
DiGeorge Syndrome is a deletion at
22q11
232
condition that causes thymic hypoplasia, hypocalcemia, congenital heart defects
DiGeorge
233
7q11.23 deletion
Williams Syndrome
234
Williams Syndrome is a deletion at
7q11.23
235
coctail party personality with low IQ, cardio defects
Williams Syndrome (7q11.23 microdeletion)
236
duplication of PMP22 gene
Charcot-Marie-Tooth Disease type I
237
what causes Charcot-Marie-Tooth disease?
duplication of PMP22 gene
238
mechanism of Charcot-Marie-Tooth Disease
increased PMP22 in PNS results in demyelinating peripheral neuropathy
239
in Charcot-Marie-Tooth Disease, sx present by age __ and include...
20
atrophy of lower leg mm., progressive weakness, foot deformities
240
PMP22 is produced by _____
Schwann Cells
241
chromosome inversion that does NOT include the region with the centromere
paracentric
242
chromosome inversion that includes the centromere region
pericentric
243
hemophilia A results from
chromosomal inversion
244
hemophilia A results in decreased
factor VIII
245
which chromosome abnormality results in seizures
ring chromosome 14 syndrome
246
chromosomes divides perpendicular to the axis of cell division resulting in
isochromosomes
247
chromosome with 2 copies of 1 arm and none of the other arm
isochromosome
248
most common isochromosome occurs with the long arm of chromosome __
(___ Sydrome)
X
Turner Syndrome
249
duplication of long arm (q) and no short arm (p) of X chromosome
Xp isochromosome
250
what are the acrocentric chromosomes
13, 14, 15, 21, 22
251
substitution of a nucleotide that results in change of amino acid
missense
252
a change in the nucleotide sequence that results in a premature stop codon
nonsense
253
an insertion or deletion that results in change of reading frame from protein synthesis
frameshift
254
mutation in fibrillin-1 (FBN1) gene
Marfan Syndrome
255
Marfan Syndrome mutation
loss of function mutation of FBN-1
256
Marfan Syndrome causes abnormal ___ signaling
TGF-beta
257
tall stature, ectopic lentis, joint hypermobility, aortic root aneurysm or dissection
Marfan Syndrome
258
multiple phenotypic effects from a single allele or pair of alleles
pleiotropy
259
define pleiotropy
multiple phenotypic effects from a single allele or pair of alleles
260
function of fibrillin-1
sequesters TGF-beta
261
different mutations in the same gene cause the same disorder
allelic heterogeneity
262
define allelic heterogeneity
different mutations in the same gene cause the same disorder
263
inheritance pattern of Marfan
autosomal dominant
264
mutations in NF1
neurofibromatosis
265
Neurofibromatosis is a mutation in
NF1
266
multiple benign fleshy tumors or cafe au lait spots is characteristic of what syndrome and what mutation
neurofibromatosis
NF1
267
same mutation can lead to variation in clinical phenotype
variable expressivity
268
define variable expressivity
same mutation can lead to variation in clinical phenotype
269
a person with a disease-causing phenotype may or may not exhibit the disease
reduced or incomplete penetrance
270
inheritance of neurofibromatosis
autosomal dominant
271
inheritance pattern of Charcot-Marie-Tooth Disese
autosomal dominant
272
CHARGE Syndrome
Coloboma
Heart defects
Atresia of Choanae
Retardation of growth
genital underdevelopment
273
what mutation causes CHARGE Syndrome
CHD7
274
inheritance pattern of CHARGE Syndrome
autosomal dominant
275
function CHD7 gene
helicase DNA binding protein 7 regulating chromatin remodeling
276
normal CFTR facilitates rebsorption of
Cl and Na ions
277
mutations in CFTR in sweat ducts lead to
hypertonic sweat (salty skin)
278
CFTR mutations in respiratory and intestinal cells leads to
reduced Cl secretion and increased Na absorption
279
CFTR mutation causes increased intracellular ions which leads to
increase water absorption
280
CFTR mutations causes increased intracellular ions and water which causes what to the mucus
dehydrates it!
281
reduced levels of adult hemoglobin
thalassemia
282
beta-thalassemia follows what inheritance pattern
autosomal recessive
283
sickle cell disease mutation
Glu6Val
284
Glu6Val mutation leads to _____ (and what's the mechanism?)
sickel cell disease
leads to beta-globin chain that leads. toHb aggregating when O2 is absent
285
frameshift mutation in hexosamindase A gene (HEXA)
Tay-Sachs
286
mutation causing Tay-Sachs
HEXA frameshift mutation
287
mechanism of Tay-Sachs
build up of gangliosides in lysosomes of the neurons
288
there is a higher incidence of Tay-Sachs in what population
Ashkenazi heritage
289
Achondroplasia mutation
Gly380Arg mutation in FGFR3
290
Gly380Arg mutation in FGFR3
Achondroplasia
291
Gly380Arg mutation in FGFR3
Achondroplasia
292
Gly380Arg results in a GOF mutation leading to
constitutively active tyrosine kinase receptor AND inhibiting chondrocyte proliferation
293
Achondroplasia demonstrates ___ ____
incomplete dominance
294
phenotype of more than 1 allele is shown at the same time
codominance
295
ABO gene encodes...
a glycosyltransferase
296
a single disease phenotype can be caused by mutations in different loci
locus heterogeneity
297
define locus heterogeneity
a single disease phenotype can be caused by mutations in different loci
298
what 4 genes are associated with hypertrophic cardiomyopathy
MYH7
MYBPC3
TNNI3
TNNT2
299
what mutations lead to osteogenesis imperfecta
COL1A2, COL1A1
300
mutations in COL1A2 or COL1A1
osteogenesis imperfecta
301
what is affected in osteogenesis imperfecta
type I collagen
302
mutation in LDLR gene
familiar hypercholesterolemia
303
inheritance pattern of familiar hypercholesterolemia
autosomal dominant
304
new mutation that was not present in the parents' genome
de novo mutation
305
de novo mutation arises in one cell in the early embryo resulting in the mutation only being in some of the cells
mosaicism
306
explain X-inactivation
in all female cells, one X chromosome is condensed into a Barr body becoming silent
307
more affected FEMALES than males suggests what inheritance pattern
X-Linked Dominant
308
more affected MALES than females suggests what inheritance pattern?
X-Linked Recessive
309
MECP2 gene mutation
Rett Syndrome
310
inheritance pattern for Rett Syndrome
X-Linked dominant
311
without the MECP2 protein (as seen in Rett Syndrome)...
genes are inappropriately expressed during brain development
312
inheritance pattern of Vitamin D resistant Ricketts
X-linked Dominant
313
PHEX gene mutation
Vitamin-D resistant Ricketts
314
PHEX gene is involved in...
phosphate balance
315
low serum phosphate is seen in
Vitamin-D resistant Ricketts
316
inheritance pattern of Hemophilia A
X-linked recessive
317
inheritance pattern of muscular dystrophy
X-linked recessive
318
mutation causing muscular dystrophy?
DMD gene encoding dystrophin
319
Duchenne vs. Becker muscular dystrophy?
Duchenne: frameshift mutation-more severe
Becker: inframe mutation-less severe
320
there are elevated levels of ___ in Duchenne muscular dystrophy
creatine kinase
321
95% of DMD patients have
cardiac disease! (cardiomyopathy, electrocardiographic abnormalities)
322
inheritance of colorblindness
X-linked recessive
323
measure of each genotype in a population
genotype frequency
324
measure of the proportion of chromosomes that have a specific allele
allele frequency
325
Hardy-Weinberg Equation
p^2 + 2pq + q^2 = 1
326
3 reasons nonrandom mating may not occur
stratification
assortive mating
consanguinity
327
describe stratification
subgroups that have remained relatively separated (socially, geographically, etc.) mate with each other
328
describe assortive mating
choice of mate because mate possesses a specific trait (dwarfs mating with other dwarfs)
329
mutation seen in deafness
GJB2
330
describe consanguinity
related individuals mating
331
consanguinity allows...
uncommon alleles to become homozygous
332
describe genetic drift
explanation for high frequency of deleterious alleles in a population
333
describe Bottleneck effect
drastic reduction in the population size
334
describe the Founder effect
subpopulation breaks off from the larger population
335
Consanguinity in a small Amish population lead to increased occurrence of Ellis-van-Crevald Syndrome... this is an example of what?
Founder Effect
336
mutation causing Ellis-van-Crevald Syndrome
EVC, EVC2
337
describe heterozygote advantage
mutant alleles are deleterious as homozygotes but are beneficial as heterozygote
338
mutant alleles are deleterious as homozygotes but are beneficial as heterozygote
heterozygote advantage
339
what is an example of heterozygote advantage?
sickle cell and malaria
heterozygotes for sickle cell trait are more resistant to malaria
340
a variation in DNA sequence that is found in at least 1% of the population
genetic polymorphism
341
a variation in DNA sequence that is found in less than 1% of the population
rare variant
342
describe replicative segregation in mitochondria
mitoDNA and mito are replicated and RANDOMLY assigned during cell division
343
define homoplasmy (mitoDNA)
the cell contains all mutant or all normal mtDNA
344
define heteroplasmy (mitoDNA)
the cell contains a mixture of mtDNA, mutant and normal
345
4 sx of mitochondrial disorders
encephalopathy
myopathy
ataxia
retinal degeneration
346
what is MERRF? and what causes it?
Myoclonic Epilepsy and Ragged-Red Fiber disease
caused by mitochondrial disorder
347
what is MELAS Syndrome? and what causes it?
Mito encephalomyopathy, lactic acidosis, and stroke-like episodes
caused by a mitochondrial disorder
348
what causes Leigh Syndrome
point mutation in MT-ATP6 gene
349
what is LHON and what causes it?
Leber Hereditary Optic Neuropathy
point mutation in ND4 gene
350
define anticipation in regard to unstable repeat inheritance
sx become more severe or start at an earlier age as a disease is passed on to the next generation
351
expansion of CAG sequence of HTT gene
Huntington Disease
352
Huntingtons:
expansion of ___ sequence of ___ gene leading to increased ____ in the _____ protein
CAG
HTT
glutamine residues
huntington
353
inheritance of Huntingtons
autosomal dominant
354
Huntington sx
clumsiness
agitation
jerky involuntary movements
355
expansion of CGG sequence in the 5' UTR of the FMR1 gene
Fragile X Syndrome
356
Fragile X Syndrome:
expansion of ___ sequence in the ___ region of the ___ gene, this leads to silencing of the gene through _____
CGG
5' UTR
FMR1
DNA methylation
357
sx of fragile X
ID
shy personality
large testicles
358
mutation causing Myotonic Dystrophy
DMPK gene
359
DMPK gene mutation
Myotonic Dystrophy
360
Myotonic Dystrophy:
mutation in ___ that causes ___ repeat in ___ region which prevents ____
DMPK
CTG
3' UTR
mRNA transport to cytoplasm
361
the addition of epigenetic factors thhat turn. thegene off during gametogenesis
genetic imprinting
362
genes turned off during spermatogenesis
paternal imprinting
363
genes turned off during oogenesis
maternal imprinting
364
why must imprinting be reversible?
so that individuals can pass all of their genetic material on
365
chromosomal deletion in the long arm of chromosome 15 on FATHER's chromosome
Prader-Willi Syndrome
366
which gene is imprinted in prader willi?
maternal
367
chromosomal deletion in the long arm of 15 on MOTHER's chromosome
Angelman Syndrome
368
sx of Angelman Syndrome
extremely happy!
sapstic
ID
369
which gene is imprinted in Angelmans?
paternal
370
what condition results from paternal uniparental disomy of chromosome 11
Beckwith-Wiedemann Syndrome
371
what causes Beckwith-Wiedemann Syndrome
paternal UPD of chromosome 11
372
what condition results from maternal uniparental disomy of chromosome 7
Silver-Russell Syndrome
373
what causes Silver Russell-Syndrome?
maternal UPD of chromosome 7
374
timeframe for term "embryo"
implantation - first 8 weeks in utero
375
timeframe for term "fetus"
9 weeks - birth
376
timeframe for term "neonatal"
first 4 weeks after birth
377
timeframe for term "perinatal"
5 months before birth - 1 month after birth
378
timeframe for term "infancy"
first year after birth
379
timeframe for term "childhood"
between birth and puberty/adulthood
380
what is the most common cause of death in infants age 2-12 months
SIDS
381
define malformations
intrinsic abnormal development (abnormal morphogenesis)
382
what is polydactyly and syndactyly and what are they an example of
too many fingers and fused fingers
malformations
383
anencephaly and acardia are examples of
malformations
384
define disruptions
secondary destruction of previously normal structure
385
amniotic bands are examples of
disruptions
386
define deformations
structure deformed during development from external pressure (was never normal but tried to be)
387
uterine constraint and oligohydramnios are examples of
deformations
388
what is a "sequence"
cascade of anomalies set off by one initiating factor
389
what is a malformation syndrome?
constellation of congenital anomalies that cannot be explained by a single initiating event
390
describe the Potter Sequence
renal agenesis causes oligohydramnios which then causes fetal compression -->pulm hypoplasia, amnion nodosum, breech
391
what does TORCH stand for?
toxoplsma gondii
other
rubella
CMV
HSV
392
agenesis vs aplasia
agenesis: no organ and NO PRIMORDIUM
aplasia: no organ but primordium is/was present
393
what are two possible results of dysplasia of abdominal wall
omphalocele
gastroschisis
394
abdominal mm. fail to form
omphalocele
395
abdominal wall fails to form
gastroschisis
396
abdominal organs seen in chest cavity and hypoplastic lungs can insinuate a
diaphragmatic hernia
397
diaphragmatic hernias are a result of
dysplasia
398
at what period of gestation is it most dangerous for exposure to teratogens
4-5 weeks
399
what is the heart at risk of if exposed to a teratogen <6 weeks gestation
ventricular septal defect
400
when does rubella usually infect the fetus
conception - 16 weeks
401
what is the rubella embryopathy tetrad
cataracts, deafness, heart defects, ID
402
when does CMV usually infect the fetus
2nd trimester
403
sx of CMV infection in fetus (4)
microcephaly, ID, deafness, hepatosplenomegaly
404
thalidomide exposure causes what in a fetus
limb develop problems
405
valproic acid embryopathy disrupts ___ that control ____
HOX genes
craniofacial and limb formation
406
what is the most common cause of intellectual disability
Fetal Alcohol Syndrome
407
fetal alcohol syndrome causes _____ defects which leads to facial dysmorphism
neural crest migration defects
408
facial sx of fetal alcohol syndrome (3)
microcephhaly
maxillary hypoplasia
flat, thin upper lip (lack of philtrum)
409
where are Phthalates found?
in flexible plastics such as tubing in hospitals
410
babies who have been hospitalized and hooked up to tubing are at risk of what?
phthalate exposure causing testicular dysgenesis syndrome
411
in a 10 lb baby, you should think what?
maternal diabetes
412
birth wt >4,000 g
fetal macrosomia
413
bloody scalp--just deep to skin (most common)
caput succedaneum
414
hemorrhage under skin and aponeurosis (common)
cephalhematoma
415
bleeding within the cranium (not common)
intracranial hemorrhage
416
HOXD13 mutations cause
syndactyly/polydactlyly
417
HOXA13 mutations cause
hand-foot-genital syndrome
418
sodium valproate disrupts ___ cuasing ____
HOX genes
craniofacial defects
419
Retinoic acid deficiency or excess disrupts _____
HOX genes
420
PAX2 mutation causes
renal-coloboma syndrome
421
PAX3 mutations cause
Waardenburg Syndrome
422
PAX6 mutations cause
aniridia (absence of iris)
423
a single transverse palmar crease (Simian crease) can suggest what abnormality
trisomies
424
neural tube defects can be caused by
folic acid (B9) deficiency
425
genetic cause of congenital dislocation of the hip presents how?
shallow acetabulum, ligament laxity
426
what does APGAR stand for
Appearance
Pulse
Grimace
Activity
Respiration
427
premature is <__ weeks
37 wks
428
implantation in lower uterus
placenta previa
429
fusion of uterus and placenta
placenta accreta
430
what is an example of confined placental mosaicism
trisomy 7
431
what is another name for Neonatal Respiratory Distress Syndrome?
Hyaline Membrane Disease
432
what is the cause of hyaline membrane disease in neonates
deficiency of pulmonary surfactant
433
what hormones modulate surfactant synthesis
cortisol
insulin
434
what ratio can be looked at to determine maturity of lungs and where is it sampled from
lecithin-sphingolyelin ratio
sample amniotic fluid
435
a lecithin-sphingolyelin ratio >__ indicates mature lungs in neonates
2
436
a lecithin-sphingolyelin ratio <__ indicates immature lungs
1.5
437
RDS
respiratory distress syndrome
438
what are two risks of treating neonates with RDS with O2?
retinopathy
bronchopulomary dysplasia
439
why can tx of RDS with O2 cause retinopathy?
O2 therapy causes decreased VEGF and apoptosis
then when on room air, VEGF is increased and you get angiogenesis
440
the risk of bronchopulmonary dysplasia in O2 tx for RDS is arrested at what stage?
saccular
441
intestinal ischemia and elevated platelet activating factor in stool indicates
necrotizing enterocolitis
442
when does necrotizing enterocolitis usually occur
after oral feeding
443
subependymal (periventricular) hemorrhage with extension into ventricles that occurs in preterm infants
germinal matrix hemorrhage
444
transcervical vs. transplacental infections
transcervical are ascending through vagina and cervix
transplacental are hematologic
445
fifth disease
parvovirus B19
446
most common early onset (0-7 days) perinatal infection
Group B strep
447
what three things can Group B strep cause in neonates
meningitis
sepsis
pnx
448
examples of immune hydrops
Rh incompatibility
ABO incompatibility
449
where does extramedullary hematopoiesis occur and what is it in response to
liver, spleen, and lymph nodes
tissue hypoxia (anemia, hypoperfusion)
450
describe Kernicterus
non-water-soluble unconjugated bilirubin deposits in the brain after birth
451
increased levels of what are seen in kernicterus
unconjugated hyperbilirubinemia
452
prevention of kernicterus includes what
UCJ bilirubin + UV lights --> dipyrroles
453
self-mutilation
Lesch-Nyham Syndrome
454
mousy or musty
PKU
455
maple syrup
maple syrup disease
456
cataracts
galactosemia
457
cherry red macula
Tay-Sachs, GM1
458
dislocated lens
homocystinuria, Marfans
459
unexplained death of an infant <1 y/o after investigation, autopsy, and review
SIDS
460
primary vs. secondary malnutrition
primary is dietary cause
secondary is d/t a medical disorder
461
caloric deprivation with wt <60% of normal
Marasmus
462
protein deprivation and pure cab diet (presents with edema)
Kwashiorkor
463
edema seen in Kwashiorkor is d/t
low levels of serum proteins (albumin, transferrin)
464
severe trauma, burns, and sepsis can cause
Kwashiorkor-like malnutrition
465
normal cells from a tissue in the wrong place
choristoma (or heteroptopia)
466
abnormally arranged overgrowth of cells that usually develop in the given organ
hamartoma
467
what is the most common tumor of infancy
hemanigoma
468
teratoma more common in females and 10% are associated with congenital anomalies
sacrococcygeal teratoma
469
many childhood tumors are immature (primitive cells) so their names end in -______
blastoma
470
what malignancy accounts for more deaths in children than all other tumors combined?
leukemia (ACUTE LYMPHOBLASTIC LEUKEMIA)
471
most common SOLID tumor in children 0-4 y/o
CNS tumors
472
second most common SOLID tumor in children 0-4 y/o
neuroblastoma
473
most common malignant neoplasm of INFANCY (1-12 mo)
neuroblastoma
474
markers of Neuroblastoma (2) -- pediatric malignancies
N-myc amplification
elevated urinary catecholamines (VMA, HVA)
475
marker for lymphoblastic leukemia -- pediatric malignancies
TdT+
476
neural tumor with no ganglion cells
neuroblastoma
477
neural tumor with some ganglion cells
ganglioneuroblastoma
478
neural tumor with more ganglion cells and minimal-no neuroblasts
ganglioneuroma
479
small blue cell tumor that may have Homer Wright Pseudorosettes
neuroblastoma
480
distinguish between stage 4 and 4S Neuroblastoma
4: dissemination to distant LNs, bone, bone marrow, liver, skin and other organs
4S: dissemination limited to skin, liver, and/or bone marrow
481
favorable age for neuroblastomas
<18 months
482
most common malignant eye tumor of childhood
retinoblastoma
483
most common renal tumor in children
Wilms Tumor (Nephroblastoma)
484
mutation causing Wilms Tumor
WT1 mutation 11p13
485
what myeloid leukemia is most commonly associated with Down Syndrome?
acute myeloid leukemia with megakaryocytic maturation (M7)
486
is AMkL or ALL (acute lymphoblastic leukemia) more common in Down Syndrome?
ALL
487
most common lysosomal storage disorder?
Gaucher Disease
488
splenomegaly, low platelet count and anemia, Erlenmeyer flask deformities of bone (splenic and skeletal problems)
Gaucher Disease type I
489
Homer-Wrighht Rosettes are seen in what condition
Neuroblastoma
490
describe stage 4S of Neuroblastomas
localized primary tumor with dissemination limited to skin, liver, and/or bone marrow (limited to infants younger than a year!)
491
Flexner-Wintersteiner Rosettes are seen in what condition?
Retinoblastoma
492
mutations in TGF beta receptors 1 and 2 (similar changes in aorta to Marfan)
Loeys-Dietz Syndrome
493
condition with ONLY aortic and/or brain aneurysms (nothing else)
Familial Thoracic Aneurysm and Dissection Syndrome
494
COL2A1 or COL11A1 mutations that presents similar to Marfan except SHORT stature
Stickler Syndrome
495
MASS Phenotype is similar to Marfan except for there is no...
progression or aneurysm or predisposition to dissection
496
cherry red cyanosis
CO poisoning
497
mechanism of CO poisoning
>200x affinity for Hb vs. oxygen
498
Burton lines of gingiva
lead poisoning
499
radiodense lines
lead poisoning
500
basophilic stippling of RBC
lead poisoning
501
mechanism of lead poisoning
binds sulfhydryl groups of cations (i.e. Ca)
502
hematologically, lead inhibits what enzymes?
heme synthesis
(ferrochelatase and delta aminolevulinic acid dehydratase)
503
which form of Mercury is most common and where is it found
organic
contaminated fish
504
pain and dusky pink discoloration of hands and feet (term and when is it found)
acrodynia
mercury poisoning
505
mechanism of Mercury poisoning
binds sulfhydryl groups of proteins
506
where is arsenic found?
pesticides
contaminated ground water
rice, shellfish contamination
507
mechanism of arsenic toxicity
prevents pyruvate --> acetyl CoA
prevents ADP --> ATP
508
hyperkeratoses and altered skin pigmentation of hands (term and when is it found)
arsenical keratoses (arsenic poisoning)
509
arsenic poisoning increases risk of
squamous cell carinoma of hands
510
Mees lines on nails
arsenic poisoning
511
where is Cadmium found
batteries
smoking
contaminated food
512
mechanism of cadmium poisoning
binds sulfhydryl groups of proteins
competitively binds divalent cations (Ca, Zn)
513
flu-like symptoms is indicative of what acute toxicity
cadmium
514
dry-cleaning, paint removal (2)
CCl4
chloroform
515
Warfarin is a ___ antagonist affecting clotting factors ____
vitamin K
II, VII, IX, X
516
Oral contraceptives increase risk of ___ (3) and decrease risk of ____
thromboembolism, CV disease, cervical CA
endometrial and ovarian CA
517
cocaine blocks reuptake of
dopamine (CNS)
E and NE (SNS)
518
amphetamines are ___ stimulants
sympathhomimetic
519
describe 1st-4th degree burns
1st: superficial, painful, no blistering
2nd: superficial-deep dermis, painful, blister
3rd: entire dermis into subQ, painless
4th: full thickness thorugh subQ
520
severe acute burn injury can cause
hypovolemia
521
two types of exertional hyperthermia
heat cramps
heat exhaustion <40 degrees
522
type of nonexertional or exertional hyperthermia
failure of thermoregulation >40 degrees
523
hypothermia
<35 degrees
524
low dose ionizing radiation causes
hematopoietic issues (risks of infection)
525
mid dose of ionizing radiation causes
intestinal issues (diarrhea)
526
high dose of ionizing radiation causes
brain damage (BBB compromised)
527
condition d/t caloric deprivation
marasmus
528
condition d/t protein deprivation
kwashiorkor
529
cachexia is d/t
hypercatabolic state secondary to TNF-alpha
530
self-induced starvation with presentation like severe acute malnutrition
anorexia nervosa
531
binge eating and induced vomiting
bulimia
532
functions of vitamin A
vision
lipid metabolism
fight infection
regulates growth and differentiation
533
three effects of vitamin A deficiency
keratomalacia
keratinizing metaplasia
papular follicular rash
534
outline vitamin D metabolism
converted to 25(OH)D in the liver
converted to 1,25-dihydroxyvitD in the kidney (active)
stimulates expression of RANKL-->regulates osteoclasts
535
vitamin D deficiency is kids vs adults
Rickets vs Osteomalacia
536
sx of vitamin C deficiency
bleeding gums, skin, joints
impaired wound healing
537
metabolic syndrome (4)
obesity
dyslipidemia
HTN
insulin resistance
538
low fiber + high animal fat puts you at risk for
colon cancer
539
how to reduce risk of atherosclerosis
decrease saturated animal fat
restrict dietary sodium
