Glossary of Path Chapter 1
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- How does mitochondrial damage occur?
- High conductance channels form in inner mitochondrial membrane which dissipates proton gradient. Cytochrome C also leaks out into cytosol and activates apoptosis.
- What is the function of cytochrome C?
- activates apoptosis
- What is the "mitochondrial permeability transition"?
- Pathologic high conductance channels formed on inner mitochondrial membrane.
- What are the 4 actions caused by increased cytosolic Ca++?
- 1) Decreased ATP via ATPases
2) Decreased phospholipids via phospholipase
3) Disruption of membrane and cytoskeletal proteins via proteases
4) Nuclear chromatin damage via endonucleases
- What 3 factors cause mitochondrial permeability transition?
- 1) increased cytosolic Ca++
2) oxidative stress
3) lipid peroxidation
- True/False: Ischemia injures tissues slower than hypoxia?
- False, ischemia injures tissues faster.
- What is the first effect that hypoxia has on a cell?
- Reduced ATP generation due to reduced oxidative phosphorylation.
- What are the major effects of decreased ATP synthesis by cells?
- 1) Cellular swellin/blebs/loss of microvilli/ER swelling due to decreased Na/K pump activity
2) chromatin clumping due to decreased pH due to increased glycolysis
3) lipid deposition due to decreased protein synthesis due to detachment of ribosomes from ER.
- What causes ribosomes to detach from Rough ER?
- 1) decreasing pH
2) decreasing ATP
- What are the 3 major mechanisms that can cause ischemia/reperfusion injury?
- 1) calcium bathing of compromised cells
2) reperfusion resuts in increased local inflammation
3) damaged mitochondria are unable to completely reduce oxygen which leads to free-radical production (antioxidant mechanisms are also compromised)
- What are free radicals?
- chemical species with a single unpaired electron in an outer orbital
- How are free radicals generated?
- 1) redox reactions
2) from NO
3) absorption of radiant energy
4) metabolism of exogenous chemicals
- What are the 3 ways that free radicals cause cell injury?
- 1) lipid peroxidation of membranes
2) DNA fragmentation
3) cross-linking of proteins
- How do free radicals damage lipid membranes?
- Double bonds in membrane polyunsaturated lipids are vulnerable to attack by oxygen-derived radicals.
- What is a harmful byproduct of lipid-radical interactions?
- How do free radicals cause DNA fragmentation?
- By reacting with thymine in nuclear and mitochondrial DNA to produce single-strand breaks.
- How do free radicals cause the cross-linking of proteins?
- By promoting sulfhydryl-mediated protein cross-linking.
- What are the 4 ways that cells inactivate free radicals?
- 1) superoxide dismutase
4) endogenous antioxidants
- What reaction does superoxide dismutase catalyze?
- forms hydrogen peroxide from superoxide (O2-)
- What reaction does glutathione peroxidase catalyze?
- breakdown of hydroxide radical to water
- What reaction does catalase catalyze?
- The degeneration of hydrogen peroxide into water and oxygen
- Where is catalase found?
- What are the 2 general mechanisms that allow chemicals to damage cells?
- 1) Directly combining with molecular components/organelles
2) By being converted to toxic metabolites that can act on target cells.
- How does mercuric chloride poisining work?
- Acts on membrane sulfhydryl groups to
1) Inhibit membrane ATPase dependent transport
2) Increase membrane permeability
- How does carbon tetrachloride damage cells?
- via autocatalytic membrane phospholipid peroxidation which leads to swelling and dissociation of ribosomes from SER and RER leading to reduced lipoprotien export due to inability to synthesize apoprotein.
- What molecule is most reponsible for converting chemicals to toxic substances?
- P-450 oxidase
- In what organelle is the P-450 oxidase found?
- In the smooth endoplasmic reticulum
- In what organ is CCL4 prinicapally metabolized?
- In the liver
- How does CCL4 poisining lead to fatty liver?
- Due to decreased synthesis of apoprotein leading to reduced exportation of lipoproteins and buildup of triglycerides in the cell
- What is the difference between a lysosome and a peroxisome?
- -Lysosomes get rid of macromolecules that have been phagocytosed as well as senescent organelles
-peroxisomes get rid of toxic substances such hydrogen peroxide
- What are the 2 ways that mammalian cells can degrade cellular material to undergo atrophy?
- 1) lysosomes
2) ubiquitin-proteosome pathway
- What is a morphological hallmark of cells undergoing atrophy?
- Increases in the number of autophagic vacuoles.
- What are the 2 ways that cells can undergo atrophy?
- 1) decrease in cell size
2) decrease in cell #
- What are 2 stimuli for cardiac hypertrophy?
- 1) mechanical triggers (increased muscle stretch)
2) trophic triggers (increased α-adrenergic receptor activation)
- True/False, cells undergoing hypertrophy have higher DNA content than normal cells?
- What are the 2 types of hyperplasia?
- 1) physiologic
- What are the 2 types of physiologica hyperplasia?
- 1) hormonal hyperplasia
2) compensatory hyperplasia
- What is an example of hormonal hyperplasia?
- The proliferation of glandular epithelium of the female breast at pubert and during pregnancy
- What is an example of compensatory hyperplasia?
- Occurs when a portion of a tissue is removed or diseased, as in partial liver resection
- What is the cause of most forms of pathologic hyperplasia?
- excessive hormonal or growth factor stimulation
- What is the difference between hyperplasia and cancer cells?
- Cancer cells continue to proliferate without growth factors whereas hyperplastic cells stop growing after growth factors have stopped. Additionally, cancer cells have DNA damage whereas hyperplastic cells do not.
- True/False: Metaplasia is irreversible?
- False, metaplasia is reversible
- True/False: Metaplasia arises by "genetic reprogramming" of epithelial stem cells or undifferentiated mesenchymal cells in connective tissue?
- What types of metaplasia are common in trachea and bronchi?
- Normal ciliated columnar epithelial cells are replaced by stratified squamous epithelium which is more "rugged".
- During chronic gastric reflux, what type of metaplasia occurs?
- stratified squamous becomes columnar epithelium (different than in bronchi and trachea)
- What are primary lysosomes?
- Membrane bound intracellular organelles containing a variety of hydrolytic enzymes that fuse with vacuoles containing material that needs to be ingested.
- What are the 2 types of processes that lysosomes are in involved in?
- 1) heterophagy
- What are lipfuscin pigments?
- Granules that represent indigestible material from intracellular lipid peroxidation.
- What is "induction" of SER?
- Hypertrophy of SER
- What is the purpose of enzymatic modifications in the P-450 mixed function oxidase system?
- increase the solubility of compounds to facilitate their excretion.
- What is the relationship between alcohol and barbituates?
- The use of alcohol causes hypertrophy of SER which allows the cell to more efficiently excrete barbituates thereby reducing the therapeutic levels of the barbituate.
- True/False: The # of mitochondria increase in a cell during hypertrophy?
- What are phagosomes
- phagocytic vacuoles
- What are autophagic vacuoles?
- Vacuoles that contain intracellular proteins/organelles that are to be digested.
- What is Kartegener syndrome?
- Immotile cilia syndrome, found in respiratory epithelium. Causes chronic bacterial infections due to malfunctioning microtubules in cilia
- What is the effect of colchine?
- It is a drug that prevents microtubule polymerization thereby preventing the movement of macrophages. It is used to treat gout.
- What are the functions of vina alkaloids?
- They bind the microtubules involved in mitotic spindles thereby anatgonizing cellular proliferation. They are used to prevent tumor growth.
- What are the 3 functions Heat Shock Protiens?
- 1) maintain proper protein folding
2) preventing pathologic protein aggregation
3) transporting prtoeints into intracellular organelles.
- What is another name for heat shock proteins?
- What happens when HSP's cannot fix irregularly folded proteins?
- The irregularly folded proteins are tagged and bound to ubiquitin for catabolism in proteosomes.
- What are examples under which synthesis of HSP's is increased?
- 1) After myocardial infarction
2) after neuronal ischemic injury.
- When are HSP's most ubiquitously expressed?
- When cells are undergoing sublethal stresses.
- What are the 3 general ways that cells can accrue intracellular accumulations?
- 1) increased production of an endogenous substance
2) defects in metabolism, packaging, transport, or secretion of endogenous substances
3) abnormal accumulation of exogenous material.
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