Test 3 Flashcards
localized and amenable to surgical removal; patient usually survives
benign
invasive tumor capable of destroying structures and spread to distant sites (metastasis); may result in early death of the patient
malignant
benign tumor of fibrous tissue
fibroma
benign tumor of fat
lipoma
benign glandular tumor
adenoma
benign cartilaginous tumor
chondroma
benign squamous epithelial tumor
papilloma
What are sarcomas?
malignant tumors of mesenchymal derivation (connective tissues); Examples– fibrosarcoma, chondrosarcoma
What are carcinomas?
malignant tumors of epithelial derivation; 80% of all malignancies
examples— adenocarcinoma, squamous cell carcinoma
tumors with more than one neoplastic cell type (epithelial and mesenchymal)
mixed tumors
tumors with more than one neoplastic cell type and derived form more than one germ layer
compound tumors
Which type of neoplasms are said to be differentiated (resemble tissue of origin)?
benign neoplasms
How can benign tumors cause problems?
1) secreting a substance (hormone, etc) in abundance
2) compressing vital organs
3) a few benign tumors may transform into malignant tumors
What are the hallmarks of malignancy?
invasion and metastases
What are the 2 steps involved in chemical carcinogenesis?
Tumor initiation and tumor promotion
INITIATION ALONE IS NOT SUFFICIENT FOR TUMOR FORMATION
Describe tumor initiation (In regards to chemical carcinogenesis).
an IRREVERSIBLE process involving the single application of a chemical or physical agent
Describe tumor promotion (In regards to chemical carcinogenesis).
a reversible process involving multiple applications of a promoting agent. Promoters cause cell proliferation.
Promoters are not carcinogenic.
Describe direct acting carcinogens.
They do not require metabolic activation to have their effect
Describe indirect acting carcinogens (procarcinogens)
require metabolism to produce ultimate carcinogen; generally performed by the cyt P-450 mono-oxygenate system
What is the primary target of chemical carcinogens?
DNA
How is ionizing radiation carcinogenic?
it causes strand breaks in the DNA
How is UV radiation carcinogenic?
it causes the formation of pyrimidine dimers in DNA; these are very hard to repair
Which UV rays are given credit for the observed increases in skin cancer?
UVB (280-320nm)
What are the common high risk strains of HPV that cause cancer?
Types 16, 18, and 31
The oncogenic potential of HPV can be related to products of two early viral genes:
E6 and E7
What are the cancers associated with Epstein-Barr Virus?
Burkitt lymphoma, B cell lymphomas, Hodgkin lymphoma, and nasopharyngeal carcinomas
What are the cancers associated with HPV?
cervical and penile/anal carcinoma
What are the cancers associated with HBV and HCV?
hepatocellular carcinoma
What are the cancers associated with HHV-8 (Kaposi sarcoma-assocatied herpesvirus)
Kaposi sarcoma and body cavity fluid B cell lymphoma
What are the cancers associated with helicobacter pylori?
gastric lymphomas and gastric carcinomas, MALT lymphoma (B cell lymphoma of stomach)
What are the cancers associated with HTLV-1?
adult T cell leukemia
2-naphthylamine is linked to what cancer?
urinary bladder cancer
4-aminobiphenyl is linked to what cancer?
urinary bladder cancer
Vinyl chloride is linked to what cancer?
angiosarcoma, liver cancer
Asbestos is linked to what cancer?
cancers of the pleura, peritoneum, and lungs
Chromium compounds are linked to what cancer?
lung cancer
Benzene is linked to what cancer?
cancer of lymphoid tissue
What are the hormones released in small cell carcinoma of the lungs?
ACTH, ADH-like, PTHrP
What are the hormones released in sarcoma?
insulin like hormone
What are the hormones released in ovarian teratoma?
thyroid hormones
What are the hormones released in Bronchial carcinoid?
serotonin
If a patient comes in with Acanthosis Nigricans, what cancers might you suspect them of having?
gastric, lung, uterine cancer
If a patient comes in with Dermatomyositis, what cancers might you suspect them of having?
breast, bronchogenic cancer
If a patient comes in with Hypertrophic osteoarthropathy & clubbing of the fingers, what cancers might you suspect them of having?
lung cancer
What is cachexia?
Progressive body weight loss
Body fat & lean body mass
Different from starvation
What causes cancer cachexia?
Production of cytokines and other soluble factors
TNF-a, IL-1, INF-g
What composes the staging system for tumors?
T= tumor size N= node involvement M= metasteses
A small local invasive tumor would be categorized as _____.
Stage 1
A large local invasive tumor would be categorized as ____.
stage 2
A tumor that has spread beyond the limits of operation would be categorized as ____.
Stage 4
A tumor with metastases in the lymph nodes would be categorized as _____.
stage 3
a needed component of the daily diet is missing or present in inadequate quantities
primary malnutrition
diet is adequate, but factors such as malabsorption, excess loss, an impairment in the ability to store or utilize, or an increase in the requirements results in malnutrition (GI diseases, chronic illness).
secondary malnutrition
protein in skeletal muscle - loss can be identified by a reduced circumference of the midarm
somatic compartment
- protein in liver - loss can be identified by decreased levels of albumin and transferrin in the blood
visceral component
Is the result of a diet deficient in both protein and carbohydrates
marasmus
Is the result of a diet where the majority of the calories consumed consist of carbohydrates, but protein intake is inadequate
Kwashiorkor
Have loss of protein within the visceral compartment (liver)
Subcutaneous fat and skeletal muscle mass are relatively preserved
Kwashiorkor
Patients have a loss of muscle mass and of subcutaneous fat
The proteins within the visceral component are not as depleted, so serum levels of albumin and transferrin are normal or slightly reduced
marasmus
What are some major complications of Bulimia ?
Major complications are due to repeated vomiting and laxative use
Pulmonary aspiration of gastric contents
Esophageal rupture
Electrolyte imbalances, such as hypokalemia, which cause cardiac arrhythmias
What are some major complications of anorexia?
Endocrine system effects are prominent
Decreased gonadotropin-releasing hormone causes decreased LH and FSH, resulting in amenorrhea.
Decreased thyroid hormone release causes bradycardia, constipation, and cold intolerance
Decreased estrogen levels cause a decrease in osteoblast activity and an increase in osteoclastic activity, resulting in osteoporosis
Body hair is fine and pale in appearance (lanugo)
Hypokalemia can result in cardiac arrhythmias and sudden death
What are the fat soluble vitamins
A, D, K, E
What are some of the functions of vitamin A?
Maintains normal vision when in reduced light
–Retinal is a component of rhodopsin in the rod cells in the retina
Helps in the differentiation of specialized epithelial cells, especially mucin-secreting cells
Stimulates the immune system
What are the roles of vitamin D?
Maintains plasma calcium & phosphorous concentrations; Supports cellular processes, neuromuscular function, & bone ossification; Enhances calcium & phosphorous absorption from small intestine & mobilization from bone
What are the water soluble vitamins?
B and C
What happens when you have too much vitamin D?
hypercalcemia which can lead to permanent brain damagE; And kidney stones
What is one of the earliest signs of vitamin A deficiency?
nigh blindness
What is the purpose of vitamin E?
serves as an antioxidant
What’s the role of vitamin K?
carboxylation of glutamate residues for the coagulation process
Describe vitamin D metabolism.
Vitamin D from the skin and diet are converted to 25-hydroxyvitamin D in the liver
25-hydroxyvitamin D is converted to 1,25-dihydroxyvitamin D (the active form of vitamin D) in the kidney
What do you see with vitamin D deficiencies ?
adults: osteomalacia
kids: rickets
What do you see in vitamin E deficiencies ?
Deficiency causes hemolytic anemia due to damage to the RBC membrane and peripheral neuropathy
What is the function of vitamin K?
Important in the formation of clotting factors II, VII, IX, and X, as well as Protein S and C
What is the function of vitamin C?
Hydroxylation of proline and lysine in collagen synthesis; also has antioxidant activity
What do you see in vitamin C deficiency?
scurvy
Vitamin B 1
thiamine
What do you see in thiamine (B1) deficiency?
Early: anorexia, nausea, constipation; Later: depression, peripheral neuropathy, ataxia, opthaloplegia, dementia (Wernicke’s encephalopathy)
What is the function of thiamine (B1)?
Is a cofactor in enzymatic reactions of ATP synthesis
Vitamin B3
niacin
What is the function of niacin (B3)?
act as cofactors in oxidation-reduction reactions
What do you see in niacin (B3) deficiency?
pellagra
What do you see in pellagra?
Pellagra - 3 D’s
Diarrhea
Dermatitis (hyperpigmentation of sun-exposed skin)
Dementia
Vitamin B6
pyridoxine
What is the function of pyridoxine (B6) ?
Manufacture of heme and synthesis of neurotransmitters
What do you see in pyridoxine (B6) deficiency?
Causes sideroblastic anemia, convulsions, and peripheral neuropathy
vitamin B 12
cobalamin
What is the function of cobalamin (B12)?
DNA synthesis
What do you see in cobalamin (B12) deficiency?
Megaloblastic anemia
Demyelination of the posterolateral tracts in the spinal cord
Vitamin B9
folic acid
What do you see in folic acid (B9) deficiency?
Causes megaloblastic anemia without neurologic symptoms
Increased risk of neural tube defects if present in pregnancy
What is the function of folic acid (B 9) ?
DNA synthesis
is produced by the stomach and results in increased appetite
ghrelin
is produced by endocrine cells present in the ileum and colon and decreases appetite
PYY
is secreted by adipocytes when adequate fat stores are present; results in decreased food intake, increased energy expenditure, and weight loss
leptin
Traction wound of the skin
Usually involves the epidermis only
AKA “scrape”
abrasion
Caused by blunt trauma
Damages deeper tissue, surface may be intact
Small vessel rupture with extravasation of blood
AKA “bruise”
contusion
Cause by blunt trauma
Tearing & stretching injury
Irregular edges with tissue bridging
May involve internal organs
laceration
A cutting wound made by a sharp instrument
Iatrogenic (scalpel) or accidental (glass)
Has clean edges and no tissue bridging
incision
Wound caused by a long narrow instrument Penetrating wound (entrance only) Perforating wound (entrance and exit)
puncture
(little red dots) caused by gunpowder striking the skin at high speed
stippling
What does stippling indicate?
gun shot was from a range of inches to about 3 feet
What would you see in gunshot victims where the gun was pressed against the body surface?
soot accumulation without stippling
What is damaged in first degree burns?
epidermis only
What is damaged in second degree burns?
epidermis and superficial dermis
What is damaged in third degree burns?
destroy skin. extend to subQ tissue
What is damaged in fourth degree burns?
extends into muscle or bone
3rd and 4th degree burns are characterized by what?
the lack of pain
What is the leading cause of death in burn victims?
sepsis–>organ system failure
What do you see in heat exhaustion cases?
hypovolemia due to water loss leads to cardiovascular collapse; CORE TEMP = NORMAL
What do you see in heat stroke cases?
lack of sweating; CORE TEMP = INCREASED
What is the most important mechanism in ionizing radiation injuries?
lysis of water to make free radicles
What are the late effects of ionizing radiation?
cancer, fibrosis, and atrophy
What is the most commonly altered oncogene?
Ras
What are the mechanisms by which oncogenes can be activated?
1) point mutations (RAS)
2) chromosomal translocation (BCR, c-MYC)
3) gene amplification (ERBB2 [HER2])
What cancers are associated with the oncogene HER2-neu (ERBB2)?
breast and ovarian cancers
What cancers are associated with the oncogene RAS?
bladder, colon, pancreatic, others
What cancers are associated with the oncogene ABL?
leukemias
What cancers are associated with the oncogene BRAF?
melanoma, colon cancer, and thyroid cancer
What cancers are associated with the oncogene c-MYC?
burkitt lymphoma
What cancers are associated with the oncogene N-MYC?
neuroblastoma
What cancers are associated with the oncogene cyclin D?
multiple myeloma; breast & liver cancers
What cancers are associated with the tumor suppressor gene Rb?
Retinoblastoma, breast, bladder, small cell lung CA, osteosarcoma
What cancers are associated with the tumor suppressor gene P53?
Colon, breast, bladder, lung, skin (~50% of all cancers)
What cancers are associated with the tumor suppressor gene NF-1?
neurofibromatosis
What cancers are associated with the tumor suppressor gene APC/ beta catenin?
Familial adenomatous polyposis, hepatocellular carcinomas
What cancers are associated with the tumor suppressor gene WT-1?
Wilms tumor, leukemias
What cancers are associated with the tumor suppressor gene VHL?
Renal Cancer, pheochromocytomas, CNS hemangioblastomas, others
virus replicates, but the cell is not killed (measles virus)
persistent infection
virus establishes a dormant infection (no active replication), but may reactivate later (herpesvirus)
latent infection
virus does not kill cell, but rather induces tumors (papilloma virus, EBV)
transformation (oncogenesis)
What is a limitation of serological techniques in diagnosing viral infections?
Limitations: Adaptive immune responses take time! Absence of specific Abs DOES NOT equal absence of infection!
What cancers are associated with Polyomavirus?
merkel cell carcinoma
What cancers are associated with cytomegalovirus?
glioblastoma
HPV 16 is associated with _____.
squamous cell carcinoma
HPV 18 is associated with ______.
cervical adenocarcinoma
What is the co-factor for African (endemic) Burkitt’s lymphoma?
malaria
In EBV, what does the gene EBNA2 do?
transactivates c-MYC
In EBV, what does the gene LMP1 do?
mimics CD40 in B cell activation
In Burkitt’s lymphoma, c-myc expression is induced by chromosomal translocation to Ig gene loci. Which Ig gene loci is the most common?
IgH
What is one of the main mechanisms of immune evasion used by tumors? (associated with increased morbidity and mortality)
the induction of T-reg infiltration
FDA approved antibody therapies target:
tumor antigens, angiogenesis, and immune checkpoint inhibitors
List the common oncogenes that are activated via chromosomal translocation.
BCR/ABL I
c-MYC/IgH
IgH/BCL-2
What are never sites of metastasis?
spleen and muscle
Lung cancer often metastasizes to the _____.
brain
GI cancers often metastasize to the _____.
liver
Which of the chromosome structural aberrations typically have the most sever phenotypic effects?
deletions
the inactivation of an X chromosome
lyonization
How do you determine how many Barr bodies are present?
number of X chromosomes minus 1
What is the most common form of congenital heart disease seen in down syndrome?
AV canal
Trisomy 13
Patau syndrome
cleft lip, sever mental retardation, polydactyly
Trisomy 18
Edward syndrome
clinched fist with overlapping finger; mental retardation and severe growth deficiency
microcephaly, “greek warrior” faces, cleft lip/palate
Wolf Hirschhorn
short stature, characteristic facies, cocktail party personality
Williams syndrome
What is the heart condition associated with Williams syndrome?
supra-valvular aortic stenosis
minor changes in lower face, hypoparathyroidism, thymic dysplasia, conotruncal heart anomalies
DiGeorge
cleft palate, conotruncal defects, distinct facies, schizophrenia
Shprintzen syndrome (velo-cardio-facial syndrome)
What cancers are associated with exposure to nitrosamine/ nitrate (smoked meats)?
stomach, bladder cancer
What cancers are associated with exposure to afloxin
liver cancer
Direct and indirect carcinogens are electron poor and ______ with electron rich compounds.
COVALENTLY BOND
what is the direct action of ionizing radiation on a cell?
Direct action – radiation interacts with and breaks DNA double strands
What is the indirect action of ionizing radiation on a cell?
Indirect action – radiation forms ROS that then damage the DNA
What is a LOD score?
Method for estimating recombination frequency;
Compares the likelihood of obtaining the test results if the two loci are linked, to that of pure chance
What LOD score are you looking for to confirm that ?
3 or greater (1 in 1000 the result was by chance)
What are the assumptions for HW equilibrium?
1) Randomly mating population
2) Allele frequencies will remain constant from generation to generation provided none is under selection pressure (+ or -)
3) Large population size
4) Absence of gene flow (drift)
purine to purine or pyrimidine to pyrimidine mutation
transition
purine to pyrimidine and vice versa
tranversion
What is polymorphism?
if there is a mutation that we see in over one percent of people, we call it polymorphism
random fluctuations of allele frequencies from generation to generation that take place in small, isolated populations
genetic drift
Allele frequencies established by chance in a population that is started by a small number of individuals
founder effects
What is more informative than race?
ancestry
Most common form of genetic variation in the human genome in which a single-base substitution has created 2 forms of DNA sequence that differ by a single nucleotide
Single-Nucleotide Polymorphisms (SNP)
What will you see in an Array-comparative genomic hybridization (aCGH) when the patient’s DNA contains a deletion?
more red than green which results in an orange color
What will you see in an Array-comparative genomic hybridization (aCGH) when the patient’s DNA contains a duplication?
more green than red
How do SNP arrays differ form aCGH?
A SNP array does not use control DNA, rather it compares the ratio to a group of known specimens and normalizes the data
Who invented the DNA fingerprint? When?
Alec Jeffreys; 1984
Name two types of DNA repeats that can be used for human identity testing?
Short tandem repeats, Variable Number Tandem Repeats
First DNA paternity test was when?
1983-1985
What techniques were used for the first DNA parentage test?
Multilocus probe of 25 short tandem repeats (well, the 25 were common between mother & son)
What DNA technique was used for DNA profiling in the Florida murder case?
single locus probes
DNA techniques were used to convict murderers for the first time in Florida in what year?
1987
What are FISH tests good for? What are they not good for?
Good for identifying duplication/deletions of specific loci.
Not good for detecting small changes, point mutations, etc.
Higher levels of TGFbeta1 associated with _______.
A doubling of the risk of ‘bad’ pulmonary disease (more severe CF in our context)
What is Robertsonian translocation?
fusion of two acrocentric chromosomes (acrocentric meaning they have their centromere near the end of the chromosome)
What is most often the cause of Trisomy 18?
maternal nondisjunction
When does the error that causes Trisomy 18 occur?
most frequently in Meiosis II
Describe the mechanisms by which tumor cells invade normal tissue and metastasize to distant sites.
Detachment – E-cadherin down regulated
Degradation – MMP, collagenase, stromelysins, PAF, cathespsins, heparanase
Adhesion – integrins, laminin, CD44
Motility into ECM – autocrine stimulation
When does the nondisjunction error that causes Klinefelters syndrome most frequently occur?
paternal meiosis I
When does the nondisjunction error that causes Down syndrome most frequently occur?
maternal meiosis I
