Adaptation, Injury and Death of the Cell

Question 1

Cell injury:

Answer 1

impair the ability of the cell to maintain homeostasis

Question 2

4 commons target areas of injury within the cell:

Answer 2

• Mitochondia (make ATP, energy)
• Plasma membrane (protect the inside from exposing to things in the circulation)
• Endoplasmic Reticulum (ER) (make proteins)
• Nuclei (genetic material)

Question 3

General Principles regarding cell injury:

Answer 3

1. Many diff. causes - all impair ability of the cell to maintain homeostasis
2. All parts of the cell are interdependent
3. No distinct indicator of the boundary between reversible and lethal injury (Slow process)
4. Extent of injury depend on type, duration and severity of the cause.
5. Extent of injury will depend on the type, health, adaptability of the affected cell.

Question 4

Cause of Cell Injury:

Answer 4

• Hypoxia
• Physical Injury (mechanical, thermal, electrical, radiation–>UV)
• Chemical Injury (ex. Cirrhosis caused by ethanol)
• Biological agents (infectious diseases, viruses, Bacteria)
• Immune Reactions (Cell-mediated, complement)
• Genetic abnormalities (Congenital or acquired)
• Inadequate nutrition (obesity, starvation)

Question 5

Hypoxia:

Answer 5

Inadequate access of oxygen to the cell.

Question 6

Ischemia:

Answer 6

Inadequate blood supply, lack of oxygen AND nutrients to cells. Can’t get rid of CO2 and metabolites.

Question 7

Erythrocyte impaired can cause:

Answer 7

Hypoxia. RBCs cannot carry the oxygen. Anemia and CO poisoning impair the ability of hemoglobin to transport oxygen.

Question 8

Mechanism of ATP depletion during Injury cell

Answer 8

decrease O2–> Decrease in oxidative phosphorylation (mitochondria) –> inadequate ATP production.
Lead to 1. decrease sodium pump (Swelling) 2. increase glycolysis –> decrease pH (Clumping of nuclear chromatin) 3. Detachment of ribosomes (decrease protein synthesis)

Question 9

Decrease sodium pump lead to:

Answer 9

ER and cellular swelling (dragging water inside bc sodium move in and cannot go out)
Increase Ca++ (protease activation lead to cytoskeletal damage)

Question 10

Increase anaerobic glycolysis lead to:

Answer 10

decrease glycogen, increase lactic acid, decrease pH (to compensate decrease of ATP)

Question 11

Reversible injury of Hypoxia

Answer 11

• Blebs coming off of the surface of the cell
• Autophagy by lysosomes (free radical leakage inside the cell)
• Mitochondrial and ER swelling
• Aggregation, clumping

Question 12

If the hypoxia gets worse or for longer period of time (Irreversible injury)

Answer 12

• Lysis of ER (due to free radical leakage, enzymatic digestion of cell component)
• Defects in cell membrane
• Rupture of lysosomes and autolysis
• Enzyme leakage (free radical leakage)
• Increase of mitochondrial permeability (due to high level of calcium) and Activate cell enzymes (membrane damage, nuclei damage)

Question 13

Most vulnerable cell to ischemia:

Answer 13

Neuron

Question 14

Production of Reactive O2 Species (unpaired electrons) by:

Answer 14

• Produce by all cell

- neutrophils and macrophages (during phagocytosis)

Question 15

Plasma membrane damage:

Answer 15

Loss of cellular component

Question 16

Lysosomal membrane damage:

Answer 16

Enzymatic digestion of cellular components

Question 17

A higher level of Calcium during hypoxia come from:

Answer 17

Mitochondrial, smooth ER

Extracellular

Question 18

2 main morphologic correlate of reversible cell injury are:

Answer 18

1. Cell swelling

2. Fatty change

Question 19

4 principle biochemical mechanism of cell injury

Answer 19

1. Mitochondrial damage (decrease ATP/Increase Reactive O2 species (ROS))
2. Entry of Ca++ (increase mitochondrial permeability/activation of cellular enzyme)
3. Membrane damage (loss of cellular component/enzymatic digestion of cellular components)
4. Protein, misfolding, DNA damage (Activation of pro-apoptotic protein)

Question 20

Cell injury by Free Radical :

Answer 20

1. Lipid peroxidation –> Membrane Damage
2. Protein modification –> Breakdown/misfolding
3. DNA damage –> Mutation

Question 21

Free radical can be generated by:

Answer 21

Metabolism, inflammation, air pollution, smoking, ionizing radiation, UV light

Question 22

Inactivation of free radicals by:

Answer 22

1. Enzymes intracellular (Superoxide dismutase - SOD) can convert them to harmless particles.
2. Antioxidants extracellular (contribute electrons to neutralize the free radical)

Question 23

2 types of Cell death (Irreversible cell injury)

Answer 23

1. Necrosis

2. Apoptosis

Question 24

Necrosis involves:

Answer 24

Autolysis
Inflammation (trigger by the influx of inflammatory cell due to leakage of intracellular component)

Question 25

4 types of necrosis:

Answer 25

1. Coagulative necrosis
2. Liquefactive necrosis (eg. abscess)
3. Caseous necrosis (combination of both coagulative necrosis and liquefactive necrosis) eg. tuberculosis
4. Gangrene (due to bacterial attack)

Question 26

Difference between necrosis and apoptosis:

Answer 26

There is inflammation followed necrosis and last much longer than apoptosis.

Question 27

Apoptosis is a normal part of life, but is also involves in abnormal ways in certain injuries. Apoptosis is initiated by:

Answer 27

1. Mitochondria (loss of growth factors (survival signals), DNA damage, accumulation of misfolded proteins)
2. Death Receptors on the surface of the cells (external)

Question 28

Usually, viable cell receptor (on the surface of the cell) are activated by survival signals (growth factor), it trigger:

Answer 28

production of anti-apoptotic proteins (Bcl-2 or BC-XL).

Question 29

When the cell is injure, there is lack of survival signals, it trigger:

Answer 29

Antagonist of Bcl-2 (anti-apoptotic proteins are decreased) and activation of Bax/Bak channels on the membrane of the mitochondria (lead to release cytochrome C from mitochondria (major activator of apoptosis - pro-apoptotic protein) –> caspases –>apoptosis.

Question 30

How the caspases sequence of enzyme is trigger to lead to apoptosis?

Answer 30

FASL (ligand) --> FAS (receptors) --> (receptor trimerize) FADD - FAS Activating Death Domain (inside of the membrane) --> Pro Caspase 8 --> Apoptosis
OR TNF (tumor necrosis factor) --> TNFRI --> TRADD --> FADD --> Pro Caspase 8 --> Apoptosis

Question 31

What can block the enzyme cascade sequences leading to apoptosis?

Answer 31

NF-kB (increase the gene expression and allows the cell to survive)

Question 32

End result of caspases:

Answer 32

Nucleus destoyed, cytoskeleton is brokendown, and the cell form blebs.

Question 33

Blebs are parts of the cell surrounded by its membrane. Blebs have proteins on the surface which are:

Answer 33

Ligands for phagocytosis.

Question 34

Too little apoptosis and cell proliferate can be the cause of:

Answer 34

Cancer and autoimmune disease.

Question 35

In cancer, 4 thing occurs:

Answer 35

1. Activation of oncogene encoding factor (bcl-2) preventing cell death
2. Bcl-2 is produced in abnormally large amounts
3. Signals causing programmed cell death are blocked
4. Inappropriate longevity of the cell

Question 36

In response to Endoplasmic reticulum (ER) stress, the cell can do 2 things:

Answer 36

1. Cellular Adaptation: decrease synthesis, increase the nb of chaperones to make more mature and correctly folded proteins.
2. Failure of Adaptation: Apoptosis.

Question 37

Intracellular Accumulations (Fats, carbohydrates, lipids, calcium…) is due to:

Answer 37

-Abnormal metabolism (hepatocytes accumulate lipids)
Defects in protein folding and transport (excess of abnormal protein)
-Lack of enzymes
-Ingestion of indigestible materials (ex. silica, people work with coal and stone)

Question 38

T or F: Intracellular accumulation normally lead to cell death.

Answer 38

False. Do not necessary lead to cell death, but make the cell appear strange.