Path Chapter 1

Front 1

How does mitochondrial damage occur?

Back 1

High conductance channels form in inner mitochondrial membrane which dissipates proton gradient. Cytochrome C also leaks out into cytosol and activates apoptosis.

Front 2

What is the function of cytochrome C?

Back 2

activates apoptosis

Front 3

What is the "mitochondrial permeability transition"?

Back 3

Pathologic high conductance channels formed on inner mitochondrial membrane.

Front 4

What are the 4 actions caused by increased cytosolic Ca++?

Back 4

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

Front 5

What 3 factors cause mitochondrial permeability transition?

Back 5

1) increased cytosolic Ca++
2) oxidative stress
3) lipid peroxidation

Front 6

True/False: Ischemia injures tissues slower than hypoxia?

Back 6

False, ischemia injures tissues faster.

Front 7

What is the first effect that hypoxia has on a cell?

Back 7

Reduced ATP generation due to reduced oxidative phosphorylation.

Front 8

What are the major effects of decreased ATP synthesis by cells?

Back 8

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.

Front 9

What causes ribosomes to detach from Rough ER?

Back 9

1) decreasing pH
2) decreasing ATP

Front 10

What are the 3 major mechanisms that can cause ischemia/reperfusion injury?

Back 10

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)

Front 11

What are free radicals?

Back 11

chemical species with a single unpaired electron in an outer orbital

Front 12

How are free radicals generated?

Back 12

1) redox reactions
2) from NO
3) absorption of radiant energy
4) metabolism of exogenous chemicals

Front 13

What are the 3 ways that free radicals cause cell injury?

Back 13

1) lipid peroxidation of membranes
2) DNA fragmentation
3) cross-linking of proteins

Front 14

How do free radicals damage lipid membranes?

Back 14

Double bonds in membrane polyunsaturated lipids are vulnerable to attack by oxygen-derived radicals.

Front 15

What is a harmful byproduct of lipid-radical interactions?

Back 15

peroxides

Front 16

How do free radicals cause DNA fragmentation?

Back 16

By reacting with thymine in nuclear and mitochondrial DNA to produce single-strand breaks.

Front 17

How do free radicals cause the cross-linking of proteins?

Back 17

By promoting sulfhydryl-mediated protein cross-linking.

Front 18

What are the 4 ways that cells inactivate free radicals?

Back 18

1) superoxide dismutase
2) Glutathione
3) Catalase
4) endogenous antioxidants

Front 19

What reaction does superoxide dismutase catalyze?

Back 19

forms hydrogen peroxide from superoxide (O2-)

Front 20

What reaction does glutathione peroxidase catalyze?

Back 20

breakdown of hydroxide radical to water

Front 21

What reaction does catalase catalyze?

Back 21

The degeneration of hydrogen peroxide into water and oxygen

Front 22

Where is catalase found?

Back 22

Peroxisomes

Front 23

What are the 2 general mechanisms that allow chemicals to damage cells?

Back 23

1) Directly combining with molecular components/organelles
2) By being converted to toxic metabolites that can act on target cells.

Front 24

How does mercuric chloride poisining work?

Back 24

Acts on membrane sulfhydryl groups to
1) Inhibit membrane ATPase dependent transport
2) Increase membrane permeability

Front 25

How does carbon tetrachloride damage cells?

Back 25

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.

Front 26

What molecule is most reponsible for converting chemicals to toxic substances?

Back 26

P-450 oxidase

Front 27

In what organelle is the P-450 oxidase found?

Back 27

In the smooth endoplasmic reticulum

Front 28

In what organ is CCL4 prinicapally metabolized?

Back 28

In the liver

Front 29

How does CCL4 poisining lead to fatty liver?

Back 29

Due to decreased synthesis of apoprotein leading to reduced exportation of lipoproteins and buildup of triglycerides in the cell

Front 30

What is the difference between a lysosome and a peroxisome?

Back 30

-Lysosomes get rid of macromolecules that have been phagocytosed as well as senescent organelles
-peroxisomes get rid of toxic substances such hydrogen peroxide

Front 31

What are the 2 ways that mammalian cells can degrade cellular material to undergo atrophy?

Back 31

1) lysosomes
2) ubiquitin-proteosome pathway

Front 32

What is a morphological hallmark of cells undergoing atrophy?

Back 32

Increases in the number of autophagic vacuoles.

Front 33

What are the 2 ways that cells can undergo atrophy?

Back 33

1) decrease in cell size
2) decrease in cell #

Front 34

What are 2 stimuli for cardiac hypertrophy?

Back 34

1) mechanical triggers (increased muscle stretch)
2) trophic triggers (increased α-adrenergic receptor activation)

Front 35

True/False, cells undergoing hypertrophy have higher DNA content than normal cells?

Back 35

True

Front 36

What are the 2 types of hyperplasia?

Back 36

1) physiologic
2) pathologic

Front 37

What are the 2 types of physiologica hyperplasia?

Back 37

1) hormonal hyperplasia
2) compensatory hyperplasia

Front 38

What is an example of hormonal hyperplasia?

Back 38

The proliferation of glandular epithelium of the female breast at pubert and during pregnancy

Front 39

What is an example of compensatory hyperplasia?

Back 39

Occurs when a portion of a tissue is removed or diseased, as in partial liver resection

Front 40

What is the cause of most forms of pathologic hyperplasia?

Back 40

excessive hormonal or growth factor stimulation

Front 41

What is the difference between hyperplasia and cancer cells?

Back 41

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.

Front 42

True/False: Metaplasia is irreversible?

Back 42

False, metaplasia is reversible

Front 43

True/False: Metaplasia arises by "genetic reprogramming" of epithelial stem cells or undifferentiated mesenchymal cells in connective tissue?

Back 43

True

Front 44

What types of metaplasia are common in trachea and bronchi?

Back 44

Normal ciliated columnar epithelial cells are replaced by stratified squamous epithelium which is more "rugged".

Front 45

During chronic gastric reflux, what type of metaplasia occurs?

Back 45

stratified squamous becomes columnar epithelium (different than in bronchi and trachea)

Front 46

What are primary lysosomes?

Back 46

Membrane bound intracellular organelles containing a variety of hydrolytic enzymes that fuse with vacuoles containing material that needs to be ingested.

Front 47

What are the 2 types of processes that lysosomes are in involved in?

Back 47

1) heterophagy
2) autophagy

Front 48

What are lipfuscin pigments?

Back 48

Granules that represent indigestible material from intracellular lipid peroxidation.

Front 49

What is "induction" of SER?

Back 49

Hypertrophy of SER

Front 50

What is the purpose of enzymatic modifications in the P-450 mixed function oxidase system?

Back 50

increase the solubility of compounds to facilitate their excretion.

Front 51

What is the relationship between alcohol and barbituates?

Back 51

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.

Front 52

True/False: The # of mitochondria increase in a cell during hypertrophy?

Back 52

True

Front 53

What are phagosomes

Back 53

phagocytic vacuoles

Front 54

What are autophagic vacuoles?

Back 54

Vacuoles that contain intracellular proteins/organelles that are to be digested.

Front 55

What is Kartegener syndrome?

Back 55

Immotile cilia syndrome, found in respiratory epithelium. Causes chronic bacterial infections due to malfunctioning microtubules in cilia

Front 56

What is the effect of colchine?

Back 56

It is a drug that prevents microtubule polymerization thereby preventing the movement of macrophages. It is used to treat gout.

Front 57

What are the functions of vina alkaloids?

Back 57

They bind the microtubules involved in mitotic spindles thereby anatgonizing cellular proliferation. They are used to prevent tumor growth.

Front 58

What are the 3 functions Heat Shock Protiens?

Back 58

1) maintain proper protein folding
2) preventing pathologic protein aggregation
3) transporting prtoeints into intracellular organelles.

Front 59

What is another name for heat shock proteins?

Back 59

chaperones

Front 60

What happens when HSP's cannot fix irregularly folded proteins?

Back 60

The irregularly folded proteins are tagged and bound to ubiquitin for catabolism in proteosomes.

Front 61

What are examples under which synthesis of HSP's is increased?

Back 61

1) After myocardial infarction
2) after neuronal ischemic injury.

Front 62

When are HSP's most ubiquitously expressed?

Back 62

When cells are undergoing sublethal stresses.

Front 63

What are the 3 general ways that cells can accrue intracellular accumulations?

Back 63

1) increased production of an endogenous substance
2) defects in metabolism, packaging, transport, or secretion of endogenous substances
3) abnormal accumulation of exogenous material.