Week 7 + Pathology Flashcards
When you see a tumor that is necrotic, what does that tell you?
The tumor is growing too fast for its blood supply to keep up.
Is an in-situ neoplasm malignant? Is it considered cancer?
It is malignant, but it is not “cancer” because the basement membrane is keeping it confined. Given time, it will break through the BM.
What is the difference between grading and staging?
Grade is dependent on microscopic evaluation: How closely do the cells resemble the cell of origin?
Stage refers to the degree of cancer spread to lymph nodes and to distant sites.
What are the seven hallmarks of cancer?
- Self-sufficient in growth signals.
- Evades the immune system.
- Evades apoptosis.
- Immortal.
- Insensitive to growth inhibition.
- Angiogenesis.
- Metastasis.
State whether each of the following is a good prognosticator, or a bad prognosticator for breast cancer:
Her2/Neu positive
Estrogen receptor positive
Progesterone receptor positive
Her2/Neu is bad.
Estrogen and progesterone receptors are good; can be used as targets for cancer treatment.
Do most metaplastic and hyperplastic tissues eventually progress to neoplasia?
Nope
Name three organ systems that are affected by hereditary hemochromatosis (aka bronze diabetes) and clinical findings associated with each organ.
Liver: cirrhosis appears as irregular borders on CT, biopsy would show collagen and fibrosis between hepatocyte nodules.
Skin: hyperpigmentation.
Pancreas: iron accumulation in pancreas would show staining for iron. Grossly, the pancreas would be dark brown. There is also no insulin secretion due to beta cell damage, so the patient may be hyperglycemic.
How does a mutated HFE gene ultimately cause cell damage?
Too much iron uptake in the GI tract –> free iron generates a lot of reactive oxygen species –> cell damage
What is the genetic mutation involved in hereditary hemochromatosis?
Mutation in the HFE gene
What tends to accumulate in hepatocytes when metabolic processes are altered?
fat
What does oil red O stain do?
Stains fat red
Plaques are made of accumulations of ________, whereas tangles are made of ________ protein.
plaques are made of beta-amyloid, tangles are made of Tau protein
________ is “cellular trash” that can accumulate in cells that don’t divide much, such as ______ and ______ cells.
Lipofuscin can be seen in neurons and cardiac cells.
What is amyloid and how does it form?
Amyloid can form when any protein misfolds, forming beta-pleated sheets that render the protein insoluble, leading to the tendency to aggregate.
_____ protein is an insoluble amyloid protein that forms in the setting of multiple myeloma, where plasma cells make _____ that misfold and accumulate.
AL protein is the insoluble protein that is a result Ig/antibody misfolding and accumulation
In the setting of _______ _______, macrophages remain activated, releasing IL-1 and IL-6, which stimulates ______ cells to secrete ______ protein that can misfold and form insoluble aggregates of _____ protein.
in the setting of chronic inflammation, macrophages secrete cytokines and stimulates liver cells to secrete serum amyloid A (SAA protein) –> AA protein aggregations (amyloidosis)
What type of amyloidosis is characterized by mutant transthyretin that aggregates and forms ATTR proteins?
Familial amyloidosis
Which stain is used specifically for amyloid? How does it do it?
congo red stain intercalates between beta-pleated sheets and gets stuck in there
If you see positive staining with congo red polarized light apple-green birefringence on a histo slide from the brain of a patient with Alzheimer’s, what does that indicate?
There are amyloid plaques in the brain.
In the development of amyloidogenesis, there is an enzymatic switch from _________ to ________, resulting in the release of __________ peptides that form aggregates –> amyloid fibrils.
enzyme switch from alpha-secretase to beta-secretase –> A-beta peptide release –> A-beta aggregates –> amyloid fibrils
Are prions normally found in neurons?
Yeah
When the normal neuronal PrP protein undergoes a conformational switch, the ________ domains switch to _______ domains, and confers the prion’s ability to convert other prions to the insoluble form.
alpha-helical domains switch to beta-sheet domains –> insoluble prions
True or false: Insoluble prion fibrils cause metabolic stress that kill neurons, resulting in spongiform encephalopathy.
Tru dat
What is the difference between dystrophic and metastatic calcification?
Dystrophic calcification occurs in necrotic tissues; calcium from the serum (normal levels) deposits into dead tissue.
Metastatic calcificationis deposition in normal tissues due to hypercalcemia.
Can you find dystrophic calcification in a lung infected with TB?
Yeah
What do you call focal, lamellar areas of dystrophic calcification seen within a tumor?
Psamonna bodies
At the cellular level, what is the cause of Gaucher’s disease? Name three clinical findings.
Mutation in the beta-glucosidase lysosomal enzyme –> buildup of substrate, especially in leukocytes.
Clinical findings: splenomegaly, hepatomegaly, bone lesions
Explain why epidermolysis bullosa is an example of a dominant negative mutation.
One mutant copy of the gene for keratin results in a protein product that disrupts the ability of the normal keratin to polymerize, so the whole thing is screwed up –> blistering
What are the two major pathways of protein catabolism?
- Ub-proteasome
2. Autophagy and endolysosomal system
Which system of protein catabolism is involved in protein synthesis quality control?
Ub-proteasome
In the Ub-proteasome pathway, which specific enzyme is responsible for protein recognition as well as the final ubiquitination step?
E3
Is ubiquitination an energy-dependent process? What about protein unfolding by the proteasome?
Both use ATP
In the autophagic system, intracellular substrates are taken up by a(n) __________, which then fuses with a lysosome for subsequent degradation.
autophagosome
Are autophagic processes upregulated during starvation?
Yeah
Lysosomal pro-enzymes are synthesized in the rough ER; at the cis-golgi, a _________ is put on the carbohydrate-end of the enzyme that serves as a signal to go to the lysosome.
mannose-6-phosphate
Describe the process of mannose-6-phosphate receptor recycling. Also describe the mechanism by which enzyme replacement therapy works.
Inside the trans-golgi, the M6P-tagged enzyme binds to the M6P receptor on the inner golgi membrane, which triggers clathrin-mediated budding from the golgi. The recently-budded clathrin-coated vesicle slowly matures into an early endosome, and then a late endosome, acidifying along the way. Low pH tiggers the receptor to bud off from the late endosome. The vesicle with the receptor then goes to the plasma membrane or back to the golgi.
The receptors that go to the plasma membrane can take in any extracellular enzymes with the mannose-6-P tag - this is the basis for enzyme replacement therapy.
Are lysosomal enzymes active at high pH?
No, they’re active at low pH!
How is the endosome acidified?
By the V-ATPase that uses ATP to pump protons into the endosome.
What determines whether something will be destroyed by the proteasome or stored in the multivesicular body?
The length of the Ub chain on the protein.
Do lysosome-related organelles serve a wide variety of functions depending on cell type?
Yeah
Does the APO-E genotype cause Alzheimer’s?
No, it is a risk factor.
True or false: Life expectancy in the U.S. is low, but is increasing faster than most other wealthy countries.
False. U.S. life expectancy is increasing at a slower rate than other wealthy countries.
How does the health of educated, white, high-income folks in the U.S. compare to equivalent groups in other wealthy countries?
People in equivalent groups in other countries are healthier!
Medical error is the _____ leading cause of death in the U.S.
third
What effect does enrolling extraordinarily healthy people have on both the internal and external validity of a clinical trial?
Increases internal validity but decreases external validity
Define “numbers needed to treat” and how it is calculated.
Numbers needed to treat estimates how many patients would need to be treated to prevent or produce a downstream clinical outcome.
= 1 / risk difference
Would a very effective drug yield a higher “numbers needed to treat” value than a less effective drug?
No, good drugs should result in a low “numbers needed to treat” value
True or false: lack of use of intention-to-treat statistical analysis jeopardizes the internal validity of a trial.
Tru dat
What is the formula for relative risk?
incidence proportion of group 1 / incidence proportion of group 2
What is the formula for risk difference?
Absolute risk in group 1 - Absolute risk in group 2
What is the formula for numbers needed to treat?
1 / absolute risk difference
True or false: the doubling time for tumor cells is longer than that of normal cells.
True!
Name four common sites of tumor metastasis.
Liver, brain, bone lungs
