Patho Unit 2 Flashcards
Understand: - Genes and Genetic Diseases (Ch 2) - Biology, Clinical Manifestations, and Treatment of Cancer (Ch 9)
1
Q
Mutation
A
Noticeable changes in an organism
2
Q
Reading Frame
A
3 bases at a time are read
3
Q
Point Mutations
A
- Do not change the reading frame
- Change only a single base, not the entire molecule
- Sometimes these change the protein sequence (Missense and Nonsense mutations)
4
Q
Missense Mutation
A
- Point Mutation
- A change from one amino acid to another
5
Q
Nonsense Mutation
A
- Point Mutation
- A codon change from an amino acid to a stop codon
- Results in an abnormally short protein
6
Q
Frameshift Mutation
A
Changes the reading frame
- Affects the entire molecule
- Caused by an insertion or deletion of one or more base pairs in the DNA
7
Q
Deletion Mutation
A
Frameshift mutation
- One base is removed
8
Q
Insertion Mutation
A
Frameshift mutation
- One base is added
9
Q
Mutagens
A
Agents known to increase the frequency of mutations
- Ionizing radiation, chemical agents, UV radiation, viruses
10
Q
Base-pair Substitution
A
- One base pair is replaced by another
- Can result in a change in the amino acid sequence
- If no change occurs it is a Silent Substitution
11
Q
Mutational Hot Spots
A
Regions of DNA that are often mutated
12
Q
Autosomes
A
In humans, chromosomes 1-22
13
Q
Sex Chromosomes
A
- Homologous pair (XX)
- Non-homologous pair (XY)
14
Q
Euploid
A
Cells that have a multiple of the normal number (23) of chromosomes
(ex: Diploid and Haploid)
15
Q
Triploid
A
A fetus has 3 copies of each chromosome
- The fetus can’t survive
16
Q
Tetraploid
A
A fetus has 4 copies of each chromosome
- The fetus can’t survive
17
Q
Aneuploid
A
A cell that does NOT contain a multiple of 23 chromosomes
18
Q
Trisomy
A
A cell containing 3 copies of one of the chromosome “pairs”
- Some infants can survive with a trisomy of certain chromosomes
19
Q
Monosomy
A
A cell containing only one of any of the chromosome “pairs”
- More often lethal
20
Q
Disjunction
A
Distributes equal amounts of genetic material to each gamete during meiosis
- Normally one copy of each gene ends up in each gamete
21
Q
Nondisjunction
A
During meiosis the 2 chromatids don’t separate creating a Trisomy or a Monosomy
22
Q
Down Syndrome
A
Trisomy 21
- Closely related to maternal age
- Causes mental retardation, low nasal bridge, epicanthal folds, protruding tongue, poor muscle tone
23
Q
Turner Syndrome
A
45, X
- Females with only one X chromosome
- Absence of ovaries, short stature, webbed neck, underdeveloped breasts, wide nipples
- A high number of fetuses are aborted
24
Q
Klinefelter Syndrome
A
47, XXY (2 or more X chromosomes and one Y)
- Male appearance
- Develop female like breasts
- Small testes
- Sparse body hair
- Long limbs
- Abnormalities increase with each additional X
25
Triplo-X
47, XXX
- Phenotypically female
- Sterility, menstrual irregularity and/or mental retardation
- Symptoms worsen with each additional X
26
Deletions
Breakage resulting in loss of DNA
| (ex: Cri du Chat Syndrome
27
Cri du Chat Syndrome
- "Cry of the cat"
- Deletion of short arm of chromosome 5
- Low birth weight, mental retardation, microcephaly (small head), shrieking cry
28
Inversions
Breakage followed by a reversal of the fragment during re-insertion
29
Duplications
Replication of a gene sequence resulting in an amino acid sequence being repeated multiple times
30
Translocations
The interchanging of material between non-homologous chromosomes (13-14, 2-5)
- Occurs when 2 chromosomes break and the segments are rejoined in an abnormal arrangement
31
Genotype
The genetic makeup of an organism
| - "What you have"
32
Phenotype
Can be a visible observation, or it can be tested for
| - "What you show"
33
Penetrance
The proportion of individuals of a particular genotype that express its phenotypic effect in a given environment
34
Expressivity
The variable expression of the disease which is caused by modifier genes
35
Sex/X-Linked Recessive Diseases
- Almost all x-linked disorders are
- Males can't be carriers, females don't express it
- Affected males won't pass it onto sons but daughters will at least be carriers
- Sons Hemophilia A and red-green color blindness
36
Sex/X-Linked Dominant Diseases
- Rare
| - Expressed in both sexes, greater incidence in females
37
Polygenic Traits
Traits involving multiple genes (hair and eye color, height)
| - For Aa and Bb (2 genes) there are 8 combinations
38
Environment
Diets, habits, and exposures
| - Have a profound influence on a large number of diseases and disorders
39
Threshold Model
There is a QUALITATIVE THRESHOLD at which the disease manifests
- You either have it or you don't (you can't be a little bit diabetic)
40
Liability
- Increases as the number of genetic and/or environmental risk factors increase
- When liability reaches a threshold a disease results
41
Recurrence Risk for Multifactorial Diseases
Because of various influences, it's difficult to calculate
42
Recurrence risk increases if...
- More than one family member is affected
- The expression in the proband more severe
- The proband is of the less commonly affected sex (woman has a heart attack)
43
Neoplasm
New and abnormal development of cells that don't respond to normal growth and control mechanisms
- Not all are cancer
44
Benign Neoplasms
- Slow growth
- Encapsulated
- Non-invasive
- Well differentiated
- Low mitotic rate
- Do NOT metastasize
45
Malignant Neoplasms
- Rapid growth
- Non-encapsulated
- Invade local structures and tissues
- Poorly differentiated
- High mitotic rate
- DO Metastasize
46
Naming Benign Tumors
Tissue of origin + "-oma"
47
Naming Malignant Tumors
Benign tumor name + modifier (blast, multiple, malignant, carci-, sarc-,)
48
Malignant Epithelial Tissue Neoplasm (name)
Carcinoma
49
Malignant Connective Tissue Neoplasm (name)
Sarcoma
50
Malignant Lymphatic Tissue Neoplasm (name)
Lymphosarcoma
51
Carcinoma In Situ
CIS
- Pre-invasive epithelial malignant tumors
- Localized in the epithelium and has not broken through the basement membrane
52
Transformation
Process by which a normal cell becomes a cancer cell
| - Not a single event
53
Anaplasia
Cells stop developing
- Loss of differentiation
- Loss of organization
54
Philadelphia Chromosome
- Translocation between chromosomes 9 and 22
| - Present in 95% of patients with Chromic Myelogenous Leukemia (CML)
55
Tumor Markers
Anything that indicates the presence of cancer
- Any kind of cell product can be a marker (hormones, antibodies, enzymes, etc)
- Tumor-Specific Antigen
- Alteration of the genes or chromosomes in the nucleus
- Often lack specificity, sensitivity, predictability and feasibility
56
Tumor-Specific Antigen
TSA
| - An antigen found on a cancer cell membrane could be a tumor marker
57
Ectopic Hormone Production
The production of hormones by tumors of non-endocrine origin
58
Abnormal Levels of Enzymes
- Cancers don't produce new or unique enzymes, instead abnormal levels of normal enzymes are found
- Usually only detected when the tumor is very large or metastasis has occurred
59
Viral Tumor-Specific Antigen
Produced and expressed by virally-transformed cells
60
Oncofetal Tumor-Specific Antigens
Expressed by cells during embryonic development but are absent or low in normal adult cells
- a-fetoprotein in hepatic, pancreatic, and epithelial cancers
- Carcinoembryonic antigen (CEA) in colonic, pancreatic, and breast tumors
61
Paraneoplastic Syndromes
Signs and symptoms unrelated to the local effects/presence of the neoplasm
- Caused by substances released from the tumor or an immune response to the tumor
62
Anchorage-Independance
Continued growth even when unattached from original tissue
63
Autonomy
Cancer cell's independence from normal cellular controls
| - Cell cycle control, repair, cell growth, differentiation factors, and growth factor receptors
64
Proto-oncogenes
Unaltered, normal healthy alleles of genes that control/regulate cellular growth and differentiation
65
Oncogenes
A proto-oncogene that has been altered (mutated) by carcinogenic agent
66
Tumor-suppressor genes
Anti-oncogenes
| - Encode for proteins that inhibit cell division
67
p53 (tumor supressor) Gene Mutations
- Normally activated if cells are exposed to a hypoxic environment to activate apoptosis
- In many cancers p53 is mutated, allowing the abnormal proliferation of cells
68
Autocrine Stimulation
Cancers acquire the ability to secrete and respond to their own growth factors
- Gene amplification allows cancer cells to create numerous copies of genes and expression of gene products
69
Telemeres
Protective end caps of chromosomes, maintained by telomerase
- When lost, a cell loses its ability to divide
- Cancer cells can activate telomerase
70
Angiogenesis
- Contributes to the growth of new blood vessels
| - Through secretion of angiogenic factors, cancers can continue to enlarge
71
Chronic Inflammation
An associated risk factor for many types of cancer
- Colon cancer with inflammatory bowel disease
- Liver cancer with chronic hepatitis
- Lung cancer with asthma
72
Oncogenic Viruses
Viruses change the genetic makeup of the cell, which alters the daughter cell
- Epstein-Barr Virus: Hodgkin/Burkit lymphoma
- HPV: Cervical cancer
- Hep B: Hepatocellular carcinoma
73
Oncogenic Bacterium
Heliobacter pylori infects the stomach
| - Most common cause of peptic ulcer disease, gastric lymphomas and carcinomas (chronic inflammation)
74
Metastasis
The spread of cancer from the initial site to distant tissues
- A sequence of events
- Much harder to treat
75
Detachment
Cells break loose from their original location
76
Invasion
Local spread
- Cellular proliferation
- Barrier destruction by lytic enzymes (secretion of proteases and protease activators to digest connective tissue and eventually break through the basement membrane)
- Down regulation of cell adhesion molecules
- Increased motility
77
Intravasation
Passage into vessels (blood or lymph)
- Lymph vessels offer little resistance to single or clumps of cells
- Blood dissemination: tumor cels form leukocyte-fibrin platelet complex to protect themselves
78
Adherence in favorable sites
Metastatic cancer cells can spread throughout the body, but certain types have a preference for specific organs (aka organ tropism)
79
Organ Tropism
Factors encouraging colonization
- Growth factors from target organ
- Hormones
- Presence of tumor receptors
- Route
80
Extravasation
Leaves blood vessels and invades secondary tissue
81
Colonization
Establishment in new tissue
82
Metastasis Sequence
- Local transformation and extension
- Motility
- Angiogenesis
- Invasion
- Intravasation (blood/lymph penetration)
- Adherence at a favorable site
- Extravasation
- Colonization
83
Stage 1
- Neoplastic cells in original site
| - Well differentiated cells
84
Stage 2
- Metastatic cell in original site an local lymphatics
| - Moderately differentiated cells
85
Stage 3
- Cells in original site and distant lymphatics
| - Poorly differentiated cells
86
Stage 4
- Metastatic cells are found in many areas of the body
| - Very poorly differentiated cells
87
Vessel Invasion (effect)
Bleeding
88
Lymphatic Invasion (effect)
Lymphedema
89
Nerve Invasion (effect)
Pain, numbness, tingling
90
Bone Marrow Invasion (effect)
Pancytopenia, infection, and bleeding
91
Liver Invasion (effect)
Hepatic insufficiency
92
Pain (clinical manifestation)
- Little to none early on
- Influenced greatly by psychological responses
- Pressure
- Terminal cancer usually manifests severe pain
93
Fatigue (clinical manifestation)
Due to
- Sleep disturbance
- Biochemical changes
- Diminished activity
- Nutritional status
94
Anemia (clinical manifestation)
Reduction in red blood cell numbers
- Chronic bleeding
- Malnutrition
- Therapies
- Malignancy in blood forming organs
- Malignancy in bone marrow can cause Leukopenia and Thromboycytopenia
95
Infection (clinical manifestation)
- Most common event leading to death
- Reduction in immune function due to treatment
- Poor wound care
- Compromised patient care
96
Cachexia Syndrome
State of ill heath, wasting, emaciation, and decreases quality of life
- Present in 80% of cancer deaths
97
Chemotherapy
Intended to destroy cells in a stage of vulnerability (mitotically active cells), usually a cocktail
- Must eliminate enough cells to allow immune system to destroy the rest
98
Chemotherapy (molecular era anti cancer drugs)
Targeted therapy
- Enzyme inhibitors
- Monoclonal antibodies (directed at a specific tumor antigen)
99
Radiation
Damages DNA of rapidly dividing neoplastic cells
| - General and targeted
100
Surgical Therapy
Exclusion, debulking, palliative
101
Locus
The physical or "geographic" location of a gene along the chromosome
102
Allele
A different form or copy of a particular gene (flavor)
103
Pancytopenia
All blood counts are low
104
Leukopenia
Low white blood cell count
105
Thromboycytopenia
Low platelet count
106
Motility
The ability to move spontaneously
107
Loss of Heterozygosity
Loss of one copy (allele) of a specific chromosome region
- For the function of a tumor suppressor gene to be lost, both chromosomal copies of the gene must be inactivated (the dominant form is mutated)
