Cell Injury And Cell Death

Front 1

Oxygen deficiency interfering with aerobic oxidative respiration

Back 1

Hypoxia

Front 2

Loss of blood supply or mismatch of blood supply and tissue demand

Back 2

Ischemia

Front 3

T/F Ischemia can be caused by either impeded arterial flow or reduced venous drainage

Back 3

T

Front 4

What is most common cause of tissue hypoxia?

Back 4

Ischemia

Front 5

T/F During hypoxia, anaerobic glycolysis can continue.

Back 5

TRUE. This is why hypoxia is less severe than ischemia.

Front 6

T/F Ischemia injures tissues faster than hypoxia because delivery of both oxygenated blood and substrates for glycolysis ceases

Back 6

T

Front 7

Infarction: defn

Back 7

Irreversible injury/cell death resulting from ischemia

Front 8

What are the steps that lead to ER Swelling, cellular swelling, loss of microvilli, and blebs from ischemia?

Back 8

1) Decreased oxygen delivery meants decreased oxidative phosphorylation

2) Decreased ATP

3) Decreased activity of Na+ pump

4) Influx of Ca, H20, and Na (water follows sodium);
Efflux of K

5) ER Swelling, cellular swelling, loss of microvilli, and blebs

Front 9

What are the steps that lead to clumping of nuclear chromatin from ischemia?

Back 9

1) Decreased oxygen delivery meants decreased oxidative phosphorylation

2) Decreased ATP

3) Increased anaerobic glycolysis

4) Decreased glycogen, Increased lactic acid

5) Decrease pH

6) Clumping of chromatin in nucleus

Front 10

What are the steps that lead to lipid deposition from ischemia?

Back 10

1) Decreased oxygen delivery meants decreased oxidative phosphorylation

2) Decreased ATP

3) Detachment of ribosomes

4) Decrease in protein synthesis

5) Lipoproteins not produces, tryglycerides can't get out of the cell

6) Lipid deposition in cell

Front 11

What types of things leads to mitochondrial injury or dysfunction?

Back 11

Increased cytosolic Ca2+, Reactive oxygen species, and lipid peroxidation

Front 12

How does increased intracellular Ca2+ lead to cell damage?

Back 12

1) Causes increase in mitochondrial permeability leading to decreased production of ATP

2) Causes activation of cellular enzymes that cause damage to membranes and nucleus (e.g., phospholipases, endonucleases, etc)

Front 13

How are ROS generated?

Back 13

Incomplete reduction of O2 --> superoxide radical in presence of inflammation, radiation, chemicals, reperfusion injury, etc.

Front 14

Superoxide dismutase converts superoxide radicals to what?

Back 14

H202 hydrogen peroxide

Front 15

Glutathione peroxidase in mitochondria converts hydroxyl radical to what?

Back 15

hydrogen peroxide then to water and O2

Front 16

What does catalase do?

Back 16

Converts hydrogen peroxide to water and O2

Front 17

Where are the following found?
1) Catalase
2) Superoxide dismutase
3) Glutathione peroxidase

Back 17

1) Peroxisomes
2) and 3) Mitochondria

Front 18

What histologic abnormalities does cellular swelling due to failure of ion pumps and water influx cause?

Back 18

hydropic change (accumulation of water in the cell); vacuolar degeneration (formation of nonlipid vacuoles in cytoplasm, most frequently due to accumulation of water)

Front 19

What does early/mild injury that may be reversible look like?

Back 19

Related to reduced ox-phos with depleted ATP. Include swelling of ER and mitochondria, membrane blebbing, clumping of chromatin

Front 20

What are the two main morphologic correlates of early/mild cellular injury?

Back 20

1) Cellular swelling due to failure of ion pumps and resultant water influx

2) Fatty change, mainly in cells involved with fat metabolism

Front 21

T/F Gross morphologic changes occur early in cell death

Back 21

False. these are the last to occur

Front 22

What is the order or these in duration of injury?

A) Ultrastructural changes
B) Gross Morphologic Changes
C) Light microscopic changes
D) Biochemical alterations --> Cell death

Back 22

D, A, C, B

Front 23

Two forms of irreversible injury/cell death

Back 23

1) Necrosis
2) Apoptosis

Front 24

T/F Both necrosis and apoptosis may be physiological

Back 24

False. Necrosis is always pathological; apoptosis may be physiologic

Front 25

What happens to cytoplasm and cell membrane in necrosis?

Back 25

Loss of membrane integrity and leakage of cytoplasm; Digestion of cell by enzymes from cell's lysosomes or leukocytes; phospholipids phagocytosed and degraded to FAs

Front 26

What happens to nucleus in necrosis?

Back 26

(These changes occur due to breakdown of DNA and chromatin)

3 patterns:

Karyolysis: fading of nucleus, due to deoxyribonuclease activity

pyknosis: nuclear shrinkage and increased basophilia due to DNA condensation

karyorrhexis: fragmentation and eventual disappearance of pyknotic nucleus

Front 27

Karyolysis: defn

Back 27

fading of nucleus, due to deoxyribonuclease activity

Front 28

Pyknosis: defn

Back 28

nuclear shrinkage and increased basophilia due to DNA condensation

Front 29

karyorrhexis

Back 29

destructive fragmentation of the nucleus of a dying cell[1] whereby its chromatin is distributed irregularly throughout the cytoplasm. It is usually preceded by pyknosis and is followed by karyolysis and can occur as a result of either programmed cell death or necrosis.

Front 30

Increased basophilia is part of what phase of nuclear death?

Back 30

Pyknosis

Front 31

Why is there no proteolysis in coagulative necrosis?

Back 31

The injury causing the necrosis also destroyed enzymes

Front 32

What type of necrosis is typical of ischemic infarcts?

Back 32

Coagulative necrosis. The infarct is defined by the tissue that was supplied by the ischemic vessel.

Front 33

What happens in coagulative necrosis?

Back 33

This type is typical for ischemic infarcts. Basic tissue architecture is preserved and structural as well as enzymatic proteins are degraded. Necrotic cells are eventually phagocytozed by leukocytes that infiltrate the area.

Front 34

What happens in liquefactive necrosis?

Back 34

Usually it occurs in setting of microbial infections. Inflammatory cells release enzymes that digest/liquefy tissue. Associated with formation of pus and is typical of cerebral infarcts.

Front 35

What type of necrosis is typical of cerebral infarcts?

Back 35

Liquefactive

Front 36

What type of necrosis is characterized by Inflammatory cells release enzymes that digest/liquefy tissue?

Back 36

Liquefactive

Front 37

What does gangrene refer to?

Back 37

Usually to ischemic necrosis of a limb

Front 38

Dry gangrene is ______ necrosis while wet gangrene is _______ necrosis

Back 38

Coagulative; liquefactive

Front 39

What happens in caseous necrosis?

Back 39

Most often associated with tuberculous infection; refers to cheese-like appearance on gross exam; cells fragmented, lysed, tissue architecture not identifiable. usually surrounded by granuloma

Front 40

Type of necrosis generally found with amorphous pink material surrounding it, unidentifiable tissue architecture

Back 40

Caseous necrosis

Front 41

What happens in fat necrosis?

Back 41

Focal areas of fat destruction, found in association with acute pancreatitis, with release of lipases into pancreas and peritoneal cavity, also, any traumatized fatty tissue. Adipocyte membranes liquefied, released fatty acids combined with calcium (fat saponification)

Front 42

Acute pancreatitis is likely to demonstrate what type of necrosis?

Back 42

Fat necrosis due to release of lipases into peritoneal cavity

Front 43

What happens in fibrinoid necrosis?

Back 43

Usually seen in immune reactions involving blood vessels; Deposition of antigen-antibody complexes in vessel wall; fibrin leaks out of vessel; bright pink, amorphous appearance ("fibrin-like")

Front 44

What does the bright pink/fibrin-like appearance represent in fibrinoid necrosis?

Back 44

Immune complexes

Front 45

Type of necrosis most likely seen in immune reactions involving blood vessels

Back 45

Fibrinoid

Front 46

Type of necrosis almost always in vessel walls

Back 46

Fibrinoid

Front 47

T/F Liquefactive necrosis leads to dissolution of the cell outline

Back 47

T

Front 48

Type of necrosis usually related to TB or fungal infection

Back 48

Caseous

Front 49

T/F Apoptosis requires energy

Back 49

T. This means it's NOT associated with ATP depletion

Front 50

T/F In apoptosis the cell membrane bursts

Back 50

False. It's largely maintained.

Front 51

What is characterized by nuclear dissolution, fragmentation of the cell, followed by removal of cell debris?

Back 51

Apoptosis

Front 52

What are the two major apoptotic pathways?

Back 52

1) Mitochondrial (intrinsic)
2) Death receptor (extrinsic)

Front 53

T/F In apoptosis, you will see little fragments microscopically

Back 53

T

Front 54

What are caspases?

Back 54

Very important proteins for initiating apoptosis