Lecture 5: Cellular response to stress Flashcards
What are the 4 core aspects of diseases?
- Etiology
- Pathogenesis
- Morphologic changes
- Clinical manifestations
What 4 factors lead to cell injury?
- Limits of adaptive responses are exceeded (cells are burned out)
- Cells exposed to injurious agents/stress
- Cells don’t have proper nutrients
- Cells are impacted by genetic mutations
What happens to cellular proteins with hypertrophy?
There is an increase in their production
What is hyperplasia?
Increase in number of cells
When does hyperplasia start and stop?
It occurs when there is a stimulus and ends when the stimulus ends
Do hypertrophy and hyperplasia often happen at the same time?
Yes
What is the definition of atrophy?
There is a reduction in the tissue or organ size due to decrease in cell size and number
Know autophagy
A cell eats its own contents, such as those that accumulate during aging, stress or disease
What is metaplasia? How does this impact underlying stem cells?
Reversible change in which one differentiated cell type is replaced by another, whereby stem cells are differentiated to replace cells that are needing to be replaced.
What is a common cause of cell injury?
Hypoxia
What are the two principle pathways of cell death?
Apoptosis and necrosis
What does necrosis lead to in regards to the structure of the cell?
- Denaturation of the intracellular enzymes
2. Loss of membrane integrity
Know the difference between polymorphisms and mutations
Polymorphisms are common differences in DNA sequence that don’t have to lead to disease, while mutations more likely result in changes
What is coagulative necrosis? What is it often associated with?
It is the architecture of dead tissues and cells preserved for a few days; it is often associated with ischemia secondary to an obstructed vessel
What is liquefactive necrosis? Where is it typically seen?
Enzymatic digestion of dead cells results in liquid viscous mass, and seen mostly in brain infarcts
What is caseous necrosis, what disease is it typically associated with, and what is its pattern of inflammation called?
“Cheese-like”, often seen in tuberculosis, called granuloma
With what types of diseases do you typically see fibrinoid necrosis?
Normally seen in immune reactions with blood vessels (like vasculitis)
What are the three major causes of ATP depletion?
- Reduced supply of oxygen and/or nutrients
- Mitochondrial damage
- ADP
What ion can result in cell death by accumulating in the mitochondria and opening mitochondrial permeability transition pores?
Calcium
What is the most common cause of cell injury in clinical medicine?
Ischemia
What three reasons is reperfusion of ischemic tissue dangerous?
- Increased generation of reactive oxygen and nitrogen species (perhaps free radicals and nitrite species)
- Intracellular calcium overload
- Inflammation/activation of complement system
The activation of caspases results in apoptosis. What are these enzymes activted by? (2 possibilities)
Activated by the mitochondria or death receptor pathways
In mammalian cells, what pathway is the major mechanism of apoptosis?/
Mitochondrial pathway
The TP53 gene is termed what, and what type of protein does it encode?
“Tumor suppresor gene”, which encodes a P53 protein in cells when DNA is damaged
What are 3 ways that cells protect against having too many misfolded proteins?
- Increased ER chaperone protein production (chaperones help protein folding)
- Enhanced destruction of misfolded proteins
- Slowed protein translation
What is special about necroptosis?
It is cell death that acts like apoptosis mechanistically, but appears necrotic morphologically
How is necroptosis triggered, and what is it characterized by?
Triggered genetically, and characterized by the plasma membrane rupturing, cell/organelle swelling and ROS generation
What are 2 examples of diseases resulting from necroptosis?
- Steatohepatitis
2. Acute pancreatitis
What are the 4 main pathways for abnormal intracellular accumulation?
- Inadequate removal of normal substance
- Accumulate abnormal endogenous substances
- Not degrading metabolites
- Depositing or accumulating abnormal exogenous substance
What is steatosis? Where is it often seen?
Abnormal intracellular accumulation of triglycerides, often seen in the liver (major organ for fat metabolism)
What is atherosclerosis and what is it associated with?
Intracellular cholesterol accumulation within the intimal layer of aorta and large arteris; associated with hypercholesterolemia
What are xanthomas and what are they associated with?
Intracellular cholesterol accumulations in skin and tendons, associated with hypercholesterolemia
What is antracosis?
Blackening of lungs and lymph nodes
Metabolism of what two substances results in color changes seen in healing bruises?
Heme and iron metabolism
What is dystrophic calcification? Where can you see this?
Calcium deposition in dying tissues; seen in aging/damaged heart valves
Name two disorders related to metastatic calcification?
Hyperparathyroidism and renal failure
Warner syndrome is characterized by what type of defective enzyme?
Defective DNA helicase
What is a major mechanism of replicative senescence?
Progressive shortening of telomeres
What two cells have telomerase, and what type does not?
Expressed in germ cells and minutely in stem cells, but not in most somatic cells
What two benefits occur from calorie restriction?
- Attenuates growth factor signaling
2. Increase in sirtuins (increase longevity)
