Term
| Three triggers for thrombus formation. |
|
Definition
Direct injury to vessel walls
stagnation of blood flow
hypercoagulative state (autoimmune or genetic) |
|
|
Term
| What are the two factors that can initiate the clotting cascade? |
|
Definition
| Hageman factor (inflammatory response), tissue factor 8 (released by platelets) |
|
|
Term
| Role of platelets in thrombus formation. |
|
Definition
| Activating thrombin and fibrinogen, recruitment of other platelets |
|
|
Term
| Which serine protease cleaves fibrinogen to fibrin? |
|
Definition
|
|
Term
| What two chemical mediators of cyclooxygenase pathway are involved in regulating thrombus formation? |
|
Definition
| Thromboxane and prostacyclin |
|
|
Term
| How does an endothelial cell negatively regulate thrombus formation? |
|
Definition
| Nitric oxide and prostacyclin secretion, physical barrier between plateletes and collagen/vWF. |
|
|
Term
| What is the major source of venous emboli? |
|
Definition
| Stasis (reduction in turbulent flow) |
|
|
Term
| Aterial emboli are primarily associated with what disease process? |
|
Definition
|
|
Term
| What does infarction mean? |
|
Definition
| Necrosis as a result of ischemic event |
|
|
Term
| How does congestive heart failure lead to generalized edema? |
|
Definition
| Reduction in blood pressure (shock) - seeping of fluid out of capillaries because of loss of blood flow/pressure |
|
|
Term
| Five types of shock and what do they have in common? |
|
Definition
Cardiogenic
hypovolemic (hemorrhage)
septic
anaphylactic
neurogenic (brain damage)
all have a reduction in blood pressure/volume, increase in vasodilation and vascular permeability |
|
|
Term
| How can you bleed to death from disseminated intravascular coagulation? |
|
Definition
| Pseudo-hemophiliac state - all clotting proteins and platelets are consumed |
|
|
Term
|
Definition
| Thinning of blood vessel lumen by deposition of fats and cholesterol |
|
|
Term
| What is the unifying hypothesis for atherosclerosis pathogenesis? |
|
Definition
| Cholesterol leaked into blood vessels, oxidized cholesterol activates macrophages, cytokines released, fibroinflammatory response, "foam cell" necrosis (oxidized cholesterol not easily digested), "positive feedback" of macrophages and necrotic core formation |
|
|
Term
| What type of inflammation occurs in atherosclerosis? |
|
Definition
|
|
Term
| Structure of an atheroma. |
|
Definition
| Necrotic core, foam cells and inflammatory factors, neovascularization, fibrous cap |
|
|
Term
| How can an atheroma lead to an infarct? |
|
Definition
| Platelets form thrombi when cap ruptures, thrombi becomes embolytic, thrombus gets stuck in heart |
|
|
Term
| What can we learn about atherosclerosis and ischemic heart disease resulting in myocardial infarction from the genetic condition known as familial hypercholesterolemia? |
|
Definition
| Cholesterol unable to be uptaken, causing increase in LDL, decrease in HDLs/VHDLs, direct atherosclerosis as a result of lack of cell uptake of cholesterol - DRAMATIC effect (5-6x serum LDL) |
|
|
Term
| What are the four principle effects of ischemic heart disease? |
|
Definition
Myocardial infarct
angina
chronic congestive heart failure
sudden death |
|
|
Term
| What is the primary cause of myocardial infarction? |
|
Definition
|
|
Term
| What are the four major risk factors for Ischemic Heart Disease? |
|
Definition
Hypertension
cigarette smoking
diabetes
blood cholesterol level |
|
|
Term
| Describe the events occurring in the damaged myocardium from 12 hours to 3 months following a myocardial infarction. |
|
Definition
Necrosis of myocardial cells
leukocyte chemotaxis
inflammatory response
fibrosis formation (3 months for myocardial fibrosis) |
|
|
Term
| What are the top three cancers in terms of incidence? |
|
Definition
| 1) Breast/prostate, 2) Lung, 3) Colon/rectum |
|
|
Term
| What are the top three cancers in terms of mortality? |
|
Definition
| 1) Lung, 2) Breast/prostate, 3) Colon/rectum |
|
|
Term
| What are the three general features that distinguish benign from malignant neoplasms? |
|
Definition
| Invasion, metastasis, and appearance |
|
|
Term
|
Definition
| A reversion of differentiation in cells - characteristic of malignant neoplasms |
|
|
Term
|
Definition
| Variable in size, shape, and appearance of cells and/or nuclei - characteristic of malignant neoplasms |
|
|
Term
|
Definition
| Abundance of DNA in cancer cells, indicating malignancy |
|
|
Term
|
Definition
| Cellular abnormality is restricted to the originating tissue (early neoplasms) |
|
|
Term
| Explain the clonal origin of neoplasms |
|
Definition
| Neoplastic growth comes from the cancerous transformation of a single cell |
|
|
Term
| What type of cancer protein is Ras? |
|
Definition
| Ras is a family of genes encoding small GTPases involved in cell growth, differentiation, and survival. |
|
|
Term
| What is the significance of Ras? |
|
Definition
| Single most common oncogenic mutation location - can be transformed by a point mutation, causing the growth signal to never stop. |
|
|
Term
| What are the three mechanisms for altering protooncogenes to oncogenes? |
|
Definition
1) Change in protein structure (increase in activity or loss of regulation)
2) Increase in protein concentration (gene amplification, increased mRNA stability, gene duplication)
3) chromosomal translocation (incrased gene expression) |
|
|
Term
| How does Rb work normally and in carcinogenesis? |
|
Definition
Rb normally prevents excessive cell growth by inhibiting cell cycle progression.
In carcinogenesis, it is inactivated, allowing the cell to escape G0 and enter the cell cycle |
|
|
Term
| How does p53 work normally and in carcinogenesis? |
|
Definition
Normally, p53 activates DNA repair proteins, induces growth arrest (usually for the purpose of repair), and initiates apoptosis.
In carcinogenesis, p53's activity is either severely reduced or lacking altogether |
|
|
Term
| How does APC work normally and in carcinogenesis? |
|
Definition
Normally, APC helps control how often a cell divides, how it attaches to other cells, or whether a cell moves within or away from a tissue.
In carcinogenesis, APC causes misregulation of cadherins, altered cell migration, and chromosome instability |
|
|
Term
| What is meant by the "Two-hit hypothesis" and "Loss of heterozygosity"(LOH)? |
|
Definition
| Only one working allele of a tumor suppressor gene is necessary for its function, so both must be mutated for the cancer phenotype to appear. |
|
|
Term
| What are the five types of DNA repair mechanisms? |
|
Definition
Homologous recombination
mismatch repair
nucleotide excision repair
DNA crosslink repair
non-homologous end joining |
|
|
Term
| A genetic defect in which DNA repair mechanism is the most common cancer predisposition? |
|
Definition
|
|
Term
| How is the reactivation of telomerase thought to be related to cancer? |
|
Definition
| The lengthening of the DNA strands brought about by telomerase helps maintain the immortality of cancer cells (telomerase activation in >90% of all tumors) |
|
|
Term
| What are the three categories of carcinogens? |
|
Definition
| Viral, chemical, and physical |
|
|
Term
| How can HPV infection lead to cervical cancer? |
|
Definition
| Viral replication and gene integration leads to p53 binding and degradation by E6 protein and Rb (blocks cell cycle progression) inhibition by E7 |
|
|
Term
| What is the difference between a tumor initiator and a tumor promoter? |
|
Definition
| Initiators contribute to the transformation of normal cells, promoters amplify carcinogenic effects of initiators |
|
|
Term
|
Definition
| Reproducible, dose-dependent reaction reflecting direct action of the compound or its metabolites on a tissue |
|
|
Term
| What are the four characteristics that influence toxicity? |
|
Definition
| Absorption, distribution, metabolism, excretion |
|
|
Term
| The majority of complications associated with use of oral contraceptives are related to what vascular process? |
|
Definition
| Deep vein thrombosis (and thromboembolism) |
|
|
Term
| How is the vascular endothelium damaged during hyperthermia? |
|
Definition
| Altered vascular permeability, edema, blisters, general vasodilation, inefficient cardiac function, altered respiration, and ultimately death |
|
|
Term
| How is the vascular endothelium damaged during local hypothermia? |
|
Definition
| Endothelium lining of venules and capillaries damages small vessel permeability - activating an inflammatory response and the formation of localized edema and blisters |
|
|
Term
| Which types of burns allow for regeneration and why? |
|
Definition
| First and second - the basal cells (the source of regenerating epithelial surface cells) remain intact |
|
|
Term
| What is a common sign of reversible alcohol induced injury in the liver? |
|
Definition
| Fatty liver. As a side note, cirrhosis is irreversible |
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