Final Flashcards
(119 cards)
1
Q
What does lentigo mean?
A
Flat (growing in a linear fashion)
2
Q
What does nevus mean?
A
Nest
3
Q
What characteristics indicate that a nevus may be dysplastic?
A
Large
Irregular border
Color variation
4
Q
What can Acanthosis Nigricans be an indication of?
A
Often associated with hyperinsulinism and obesity, may rarely indicate stomach cancer
5
Q
What is the sign of Leser-Trelat?
A
Sudden appearance of multiple seborrheic keratosis lesions
6
Q
What physical exam tests are used for psoriasis and pemphigus?
A
Psoriasis: Auspitz sign. Scrape scale, get pinprick bleeding.
Nikolski’s sign: rubbing the skin quickly exfoliates outer layer and forms blister.
7
Q
What is the relationship of topical steroids and tinea infection of the skin (athlete’s foot)?
A
There are topical creams that are combination steroid/antifungal, which seem to be overused for treatment of tinea infections.
- Topical steroids may make the infection worse.
- It takes several weeks to treat tinea, so patients treated with combo products are at risk for side effects from prolonged steroid use.
- Combo products are more expensive than antifungals alone.
8
Q
What is the difference between erythema nodosum and erythema multiforme?
A
Nodosum: painful nodules on shins, associated with granulomatous dz and strep. Associated with subQ adipose.
Multiforme: vesicles, bullae, and targetoid red lesions, hypersensitivity rxn
9
Q
What layers are involved in the following skin cancers: SCC, BCC, and melanoma?
A
SCC: stratum spinosum
BCC: stratum basale
Melanoma: melanocytes in stratum basale
10
Q
On an H&E stain, which structures are red and which are blue?
A
Red (eosin) - cytoplasmic proteins
Blue (hematoxylin) - nuclear material
11
Q
What is the difference between necrosis and apoptosis?
A
Apoptosis: Programmed cell death. Clean and orderly, everything is broken down and released in vesicles to be cleared by macrophages.
Necrosis: Inflammatory cell death. Cells burst open, giving rise to local inflammation.
12
Q
What are common causes of cell injury?
A
Hypoxia, infection, immune reaction, congenital disorders, chemical injury
13
Q
What diseases arise from deficiencies in the following vitamins:
A, C, D, K, B12, Folate, Niacin
A
A: squamous metaplasia, immune deficiency, vision problems C: scurvy D: bones K: bleeding B12: anemia, neuropathy Folate: anemia, neural tube defects Niacin: pellagra,
14
Q
When does cloudy swelling occur?
A
When cell can no longer maintain ionic and fluid homeostasis.
15
Q
Where do free radicals come from?
A
Ionizing radiation, smoking, pollution, inflammation, metabolism
16
Q
Describe the pathway of injury in a cell that leads from mitochondrial dysfunction to swelling?
A
Mitochondrial dysfunction Decreased ATP --> higher mito permeability Release of cytochrome C --> apoptosis Na/K ATPase fails Influx of Na/H2O, Efflux of K Cellular swelling
17
Q
What is anaplasia?
A
Anaplastic cells completely lack differentiation and divide rapidly.
Cells lose contact inhibition (grow on top of each other) and polarity, nuclei are very large and stain dark. Increased nuclear:cytoplasmic ratio.
18
Q
What is the difference between primary, secondary, and tertiary intention?
A
Primary: wound edges approximate neatly, little scarring
Secondary: wound edges do not approximate, healing requires granulation tissue to grow in the gap, scarring and contraction
Tertiary: wound is physically prevented from healing until later, e.g. so it can be cleaned
19
Q
What is the difference between hypoplasia and agenesis?
A
Hypoplasia is defective or incomplete development of a structure.
Agenesis is complete failure to develop.
20
Q
Describe the different kinds of stem cells
A
Totipotent: give rise to all cells in body, plus placenta; only the first few divisions after fertilization
Puripotent: give rise to all cells in body; all embryonic stem cells
Multipotent: give rise to multiple cells types; adult stem cells, cord blood stem cells
21
Q
Which basic tissue types have labile, stable, and permanent cells?
A
Labile: continually dividing; epidermis, mucosal epithelium
Stable: low level of replication; hepatocytes, renal tubule epithelium, pancreatic acini
Permanent: never divide; nerve cells, cardiac myocytes, skeletal myocytes
22
Q
What are the three stages of fracture healing?
A
Procallus (anchors bones, but no rigidity)
Fibrocartilate callus
Osseus callus
23
Q
What is the difference between a traumatic fracture and a pathologic fracture?
A
Traumatic: due to a force that breaks the bone
Pathologic: secondary to another condition, like cancer
24
Q
What is a karyotype and what is an ideogram?
A
Karyotype: the set and appearance of chromosomes, often refers to a picture of the mitotic chromosomes.
Ideogram: the banding pattern on a mitotic chromosome.
**mutations must be larger than 4mb to be seen on a karyotype
25
What are the parts of a chromosome?
Long arm (q), Short arm (p), centrosome
26
How many pairs of autosomes and sex chromosomes are present in a normal human cell?
22 pairs of autosomes
| XX or XY sex chromosomes
27
Medical vs general sense of "gene"
General: any functional unit of a chromosome, any trait
Medical: a specific protein-coding sequence on a chromosome
28
What is a locus?
The exact location of a gene on a chromosome (its address)
29
What are alleles?
Two or more variants of a particular gene. Different combinations of alleles give rise to normal human variation.
30
Genotype vs Phenotype
Genotype: the combination of alleles that an individual has
Phenotype: the physical traits expressed in an individual
31
What is a SNP?
Single nucleotide polymorphism. A mutation in which two homologous sequences of DNA (usually alleles) differ by only one base.
32
What is the difference between imprinting on the X chromosome and imprinting on autosomes?
In females, one entire X chromosome is turned off with generalized methylation. It shrivels up and is never transcribed.
Imprinting on autosomes refers to the fact that a small number of genes is only transcriptionally active when transmitted by one of the sexes.
This becomes a problem if there is a deletion of the non-imprinted copy of the gene--the individual effectively lacks that gene. Examples are Angelman and Prader-Willi Syndromes.
33
What are the 5 points of control for gene expression? Which is the most studied for epigenetic influence?
Chromatin stage (most studied in epigenetics)
Transcriptional stage
Translational stage
Post-translational control into cytoplasm
Post-translational modification
34
Why does DNA naturally wrap around histones?
| What epigenetic changes occur to histone tails to encourage or discourage winding/unwinding?
DNA is negatively charged, histones are positively charged.
| Methylation and deacetylation of histone tails discourages unwinding, acetylation encourages unwinding.
35
What is a promoter region on a gene, and why are promoter regions generally not methylated?
The promoter is an upstream sequence that attracts the RNA polymerase complex to the gene.
Promoter methylation results in permanent silencing of the gene.
36
What is the difference between exudates and transudates?
Exudate: high protein content
Transudate: low protein content
Transudates result in pitting edema.
37
What is Virchow's triad, and what are examples of the diseases/conditions contributing to each of the three factors?
The three broad categories of factors thought to lead to thrombosis:
1. venous stasis (atrial fib, left ventricle dysfunction, immobility, varicose veins, venous obstruction)
2. vascular injury (trauma, venipuncture, chemical irritation, heart valve dz, atherosclerosis, catheters)
3. hypercoagulability (clotting disorders, pregnancy, oral contraceptives, nephrotic syndrome, age, IBD, malignancy)
38
What is the difference between and embolus and a thrombus?
Thrombus: a blood clot in a vein
Embolus: A mass that travels in the blood vessels until it blocks one (may be a broken off piece of a thrombus)
39
What are the features of pulmonary embolism?
Often clinically silent, arising from DVTs.
Classic presentation is postop patient who gets out of bed and collapses.
Dyspnea, tachypnea, pleural chest pain, cough + hemoptysis (coughing up blood)
40
What is the most common outcome of PE?
No sequelae and complete resolution in 75% of cases.
41
What is the newspaper test?
A quick way to determine if a fluid is transudate or exudate. If you can read a newspaper through it, it's low-protein (transudate-transparent)
42
Which countries have the highest incidence of HIV?
South Africa and Botswana (?)
43
Describe the replication cycle of HIV.
HIV infects CD4+ cells, which includes CD4+ T-cells, macrophages, follicular dendritic cells, and Langerhans cells.
GP120 on virus surface binds CD4, then GP40 binds either CCR5 or CXCR4 for the virus to enter the cell.
Virus from T cells can infect macrophages, virus from macrophages can infect T cells.
44
Why do 10% of hemophiliacs not progress to AIDS?
Some people with hemophilia have a CCR5 deletion, so they lack the CD4 coreceptor required for the HIV replication cycle.
45
What are the phases of HIV infection that lead to AIDS?
Acute phase: initial infection, viremia with reduced CD4 count, Mono symptoms + lymphadenopathy, then seroconversion (antibodies against HIV appear, virus population crashes)
Latent phase: asymptomatic/lympadenopathy, low virus in blood, minor opportunistic infections, avg 10 years
46
What two neoplasms are most commonly seen in AIDS?
```
Kaposi sarcoma (Herpes 8, endothelial cells/B cells/monocytes, skin/GI/lymph/lungs)
Non-Hodgkin lymphoma
```
47
What are the diagnostic criteria of AIDS?
HIV infection plus one of the following:
- CD4 count below 200
- CD4 less than 15% of total lymphocytes
- AIDS-defining disease
48
What are the diagnostic and monitoring tests for HIV infection?
Diagnostic: HIV antibody ELISA or Western blot
Monitoring: measure HIV RNA load via PCR
49
What are mitotic bodies and what do they tell you about a cancer?
Mitotic bodies are dividing cells spotted in histological preparation. No nuclear membrane is evident, just tangled, dark-stained threads (mitotic chromosomes)
Counting mitotic bodies can indicate if a tumor is benign or malignant.
50
In what tissues do sarcomas arise? How do they prefer to spread?
Muscle or connective tissue (mesenchymal tissue). Hematogenous spread.
51
In what tissues do carcinomas arise? How do they prefer to spread?
Epithelial cells. Lymphatic spread.
52
What are adenocarcinomas?
Tumor of epithelial cells that grows in glandular patterns.
53
Which tissues are most sensitive to ionizing radiation, and why?
Cells that:
Have high division rate, have high metabolic rate, are non-specialized type, are well-nourished.
Lymphoid organs, bone marrow, blood, testes, ovaries, intestines
54
Does the suffix -oma always mean cancer is benign?
Usually it means benign, but there are notable exceptions (i.e. lymphoma, which is malignant).
55
How does the Ames test work? How might it be misleading?
Detects possible mutagenic effect of possible carcinogens on Salmonella, this is a good proxy for in vivo carcinogenicity.
A his- culture is grown with a potential carcinogen, supplied with limited histidine. Mutations are induced (or not) by the drug, only the bugs that revert to his+ survive once the supplied histidine is used up.
May be misleading because:
1- does not test for indirect carcinogens
2- does not test for substances that exert their effect slowly over time
3- substances may not have the same effect on a prokaryote as on a human cell
56
Worldwide, which cancer kills the most women and which kills the most men?
Women: cancer of the cervix
Men: hepatocellular carcinoma
57
In the first world, in what age range does cancer incidence peak?
Peak age range: 80-84 y/o
| Low age range: 5-9 y/o
58
What are the MEN syndromes?
Multiple endocrine neoplasia: autosomal dominant inherited cancer syndromes
MEN 1 : pituitary, parathyroid, pancreas
MEN 2A: parathyroid, thyroid, adrenal
MEN 2B: mucosal neuroma, Marfan body, thyroid, adrenal
59
What is the difference between a preneoplastic disorder and a paraneoplastic syndrome?
Preneoplastic disorder: associated with increased incidence of malignant neoplasia.
Paraneoplastic syndrome: symptoms arising due to the presence of a cancer in the body; humoral, not the same as mass effect (disease due to physical pressure of tumor on other tissues)
60
What is an initiator, and what is the difference between direct-acting and indirect-acting chemical carcinogens?
Initiator: causes a mutation
Direct-acting: directly modifies DNA in ingested form.
Indirect-acting: also called a procarcinogen, requires metabolic conversion to become a direct-acting carcinogen.
61
What is the difference between the genotoxic and non-genotoxic mechanisms of carcinogenesis?
Cancer develops due to altered cell signaling. Genotoxic carcinogens damage the native DNA, while non-genotoxic carcinogens cause effects that alter signaling without actually modifying DNA (immunosuppression, chronic irritation/cell death, ROS, epigenetics, etc.)
62
What do geneticists look for when they identify a gene's promoter? Why does risk of malignancy increase with increased promoter methylation?
Look for CpG islands
Risk of malignancy increases because methylation of cytosine can mutate it to a thymine; more mutations increases chance of malignancy.
63
What type of solar radiation is most carcinogenic?
UVB
64
How does UVB cause cancer?
It produces pyrimidine dimers in DNA, leading to transcriptional errors and mutations of oncogenes and tumor suppressors
65
What type of radiation is used in radiation oncology and sterilization?
Ionizing radiation, specifically X-rays, gamma, beta, and positrons.
66
Why is neutron radiation not used?
Neutron radiation is more harmful to the normal tissue.
67
What 3 essential activities are proto-oncogenes involved in?
Synthesis of receptors
Synthesis of messenger systems
Nuclear transcription
68
What is meant by gain/loss of function mutations? How many "hits" do you need for each to create a problem?
Gain of function: oncogenes stimulate cell cycle, need ONE HIT to increase activity (make more protein)
Loss of function: tumor suppressors inhibit cell cycle, need TWO HITS to decrease activity (make zero protein)
69
What were Dr. Peyton Rous's findings relevant to cancer, and what were his methods?
Rous homogenized a chicken tumor, filtered out the cells so that only virus remained, and injected the solution into healthy chickens, which developed disease.
Discovered virus csan cause cancer.
20% of human cancers are caused by virus.
70
What is an acutely transforming retrovirus and how does it cause cancer?
Virus enters host cell and integrates into DNA at a proto-oncogene. The new viral oncogene moves to a new host cell, where it is integrated into the DNA and expressed, leading to neoplastic transformation.
71
Fred and Freda both have grade II Stage IIa adenocarcinoma of the distal esophagus. What is it about the same type of tumor at the same stage, that still may make the prognosis in these two individuals different?
As cancer cells divide, they acquire more mutations, with hundreds or thousands of mutations in every tumor. Therefore, every tumor is unique, despite similarities in gross appearance and behavior.
72
What are the 7 fundamental changes in cell physiology that make a tumor malignant?
1. self-sufficiency in growth signals (I'm doing my own thing)
2. Insensitivity to inhibitory signals (Don't tell me what to do)
3. Evasion of apoptosis (I'm invincible)
4. Limitless replicative potential (I keep going and going and going...)
5. Sustained angiogenesis (I build my own infrastructure)
6. Ability to invade and metastasize (I'm coming to get you!)
7. Defects in DNA repair (I don't even care.)
73
What is the guardian of the genome? What phase does it normally stop the cell from entering if it has damaged DNA?
p53, tumor suppressor that regulates cell cycle
Arrests cell cycle at G1 checkpoint until DNA damage is repaired.
74
What is Li-Fraumeni syndrome, and what does it cause? What year was it first described?
Germ-line mutation of p53, results in high rate of multiple types of tumors including childhood cancers.
Described 1969.
75
Apoptosis is regulated by which two genes?
p53 (stimulates apoptosis with excessive DNA damage)
| bcl-2 (inhibits apoptosis by binding CytC and Apaf-1)
76
What is fine-needle aspiration? What does it NOT give the pathologist?
A needle is inserted into the tumor to withdraw cells. Can usually indicate benign vs. malignant, but cannot assist with grading or staging as it's just cells--no architecture, no blood vessels, etc.
77
On an angiogram, how can you tell if a blood vessel is normal or caused by neoplasmic angiogenesis?
Blood vessels associated with tumors are tortuous and irregular.
78
Why are mice the animal of choice for producing monoclonal antibodies to human cancers?
The humoral human-anti-mouse reaction is particularly strong.
79
What do monoclonal antibodies specifically target in human cancers?
Tumor markers, like CA-125 (ovarian) and CA19-9 (pancreatic)
80
What is the difference between tumor grading and staging?
Grading is estimating the malignancy of the cancer. Specific for each type of tissue and cancer within it using degree of differentiation and number of mitoses. No indication of prognosis. I thru V.
Staging is estimating extent of tumor spread. Better predictor of prognosis. Uses TNM system.
81
What is Grade 4 cancer, and what is Stage 4 cancer?
Grade 4: Undifferentiated/anaplastic
Stage 4: Metastatic (regardless of T and N)
82
What would be the prognosis of grade 4, stage 4 cancer?
This is as bad as it gets.
83
In tumor progression, what does genetic instability mean? What does this mean for patients whose cancer returns, who must undergo chemo again?
Malignant cells are more likely to mutate and accumulate additional defects, meaning tumors become more malignant over time.
For patients, rapid mutation means that tumors develop under selective pressure from the environment, including treatment. This means that a recurring tumor is less likely to respond to the same treatment used before.
84
What is the difference between seeding and translation with regard to metastasis?
Seeding is a local phenomenon and not truly metastasis.
| Translation is migration of cancer cells to different tissues via the blood supply
85
Who was Sister Mary Joseph, and what principle of metastasis did she discover?
She was a surgical assistant to William Mayo. Discovered that a palpable nodule bulging into the umbilicus indicates metastasis of pelvic or abdominal cancer. The principle is that an umbilical nodule is often observed in patients with advanced metastasis.
86
What three cancers like to metastasize to brain?
Lung, melanoma, breast
87
What three cancers like to metastasize to bone?
Lung, breast, prostate
88
On an X-ray, what cancers produce osteoblastic vs osteolytic lesions?
Osteoblastic: prostate
Osteolytic: multiple myeloma, breast
89
What test can you use on physical exam to test for possible bony metastasis to the spine?
Tuning fork test:
Smack a tuning fork to make it vibrate, set it on a spinous process. If they jump (it's very painful?) metastatic disease is likely.
90
Define the following levels of cancer treatment:
| Induction, neoadjuvant, adjuvant, salvage
Induction: First Tx in protocol, or sole Tx available.
Neoadjuvant: early treatment used to shrink a tumor before the main therapy (e.g. surgery)
Adjuvant: additional modalities used after primary treatments (e.g. surgery)
Salvage: "hail mary" for tumors that fail to respond to initial Tx.
91
Which two types of tumors are very sensitive to XRT? Why?
Seminomas, lymphomas
| XRT causes damage in M phase (mitosis), and these tumors are in tissues with high turnover rate.
92
Which two types of tumors are very radioresistant? Why?
Carcinomas and sarcomas
| Cells don't divide as fast
93
What is the NCCN?
National comprehensive cancer network
An alliance of 25 top cancer centers worldwide. They compile the cutting edge of cancer care into guidelines for practitioners to access.
94
What are odors that suggest a diagnosis? What do arsenic and cyanide smell like?
Some poisons result in a particular smell on the breath.
Arsenic -- garlic
Cyanide -- bitter almonds
95
How often do patients with CO poisoning turn cherry red?
Rarely
96
What poisoning often accompanies CO poisoning in residential fires, yet was not known of until fairly recently? How is each treated?
Cyanide.
CO: hyperbaric oxygen to displace CO from hemoglobin
CN: antidote kit with amyl nitrite, sodium nitrite, sodium thiosulfate. Induce methemoglobin, which will bind CN and be excreted renally.
97
What is meant by "heavy metals"?
Any metal or metalloid of environmental concern, each described in terms of acute and chronic exposure.
98
Do radioisotopes bioconcentrate? How do they get into the air?
Yes, they bioconcentrate.
| They get into the air due to smoke from fires caused by nuclear reactor meltdown.
99
Does a bottle of wine made in 1924 contain cesium?
The answer he's looking for is "no", but in reality Cs existed, just not its radioactive isotopes (especially 137-Cs)
100
How can you increase the toxicity of Hg?
Methylmercury (methylated by soil or water organisms) is much more easily absorbed than elemental Hg.
101
What are the two main toxicities of Hg?
Neurotoxicity
| Nephrotoxicity
102
Why is arsenic poison for humans?
It disrupts ATP production through several mechanisms, including inhibiting PDH, uncoupling ETC, and competing with phosphate (as arsenate) in many reactions.
103
Compare Mees lines and lead lines.
Mees lines: transverse bands on fingernails due to chronic As exposure
Lead lines: dark lines at the gingivodental border indicating lead deposition
104
Why is lead poisoning so much more damaging to children?
Lead is neurotoxic, blocking synapses. It interferes with children's neurological development because they cannot make novel synapses.
105
What is Pica? What is basophilic stippling?
Pica: consumption of non-food substances (like dirt), common route of childhood lead poisoning
Basophilic stippling: speckles appearing at the periphery of basophils
106
Why do people who start smoking at 30 or 40 not get COPD?
Likely because smoking while young kills off lung tissue while it is still developing
107
Why is 20 pack years a notable number in lung cancer?
20 pack years and below have lower risk of lung cancer
108
What 3 illnesses are children more likely to develop due to secondhand smoke?
SIDS
Otitis media/upper respiratory infection
Asthma
109
What is photochemical smog? How is it different from the smog of 1905?
Original smog was a thick, impermeable air pollution due to burning coal in the city.
Modern (photochemical) smog is derived from vehicular emissions and industrial fumes, which react with sunlight in the atmosphere to form secondary pollutants.
110
What are VOCs? What how is ozone produced? Where does ozone go if there is air inversion?
Volatile organic compounds: organic compounds that vaporize easily.
Ozone is produced when nitrogen oxides react with oxygen in the presence of sunlight in the atmosphere. Ozone is then mixed into the rest of the pollution in the troposphere.
111
Why is silicosis the most common pneumoconiosis?
It is usually an occupational disease of miners, due to use of pneumatic drills and explosives producing large amounts of dust.
112
What is silicosiderosis?
Pneumoconiosis caused by mixed dust containing silica and iron.
113
What is Caplan's syndrome?
A combination of pneumoconiosis caused by mining dust and RA. (Also known as a huge bummer)
114
What is the difference between silica, silicates, silicon, and silicone?
Silicon: element, not found in nature
Silicone: synthetic polymer with S, H, C, and O
Silica: silicon + oxygen (quartz)
Silicates: silica + other elements
115
What are the two meanings of pathognomonic?
1. Feature is characteristic of a disease
| 2. Features absolutely defines a disease
116
In what disease are eggshell calcifications seen on CXR?
CXR = chest x-ray
| This finding is pathognomonic for silicosis in both senses of the word.
117
How do inhaled particles cause fibrosis of the lungs?
Injury to the tissue and presence of particulates recruits lymphocytes and macrophages. Activated macrophages recruit neutrophils and fibroblasts. Neutrophils further injure type I pneumocytes, leading to hypertrophy & hyperplasia of type II, which recruit more fibroblasts.
(Based on the flowchart in the notes)
118
What are the fibers of asbestosis called?
Where in the lungs do they localize?
What kind of lung cancer do they cause?
Where is this cancer, and why?
Asbestos fibers may be amphibole or serpentine.
Distal lung
Mesothelioma
The pleura. Fibers are deposited in the parenchyma of the lung, then work their way through to the pleura (?)
119
By what factor does asbestos exposure increase risk of lung cancer?
5-fold increase in risk of lung cancer
| In conjunction with cigarettes, 55-fold increase in risk of lung cancer
