Cell death, Injury

Question 1

What are the stages in cell response to stress and injury?

Answer 1

Homeostasis: normal cells have a fairly narrow range of function or steady state
Adaptation: excess physiologic or pathologic stress may force the cell to a new steady state
Injury: Too much stress exceeds the cell’s adaptive capacity

Question 2

Three groups of cells on the basis of proliferative capacity and relation to the cell cycle

Answer 2

1) Continuously dividing cells (labile cells)
2) Quiescent Cells ( Stable Cells)
3) Non-dividing cells ( Permanent Cells)

Question 3

Labile Cells

Answer 3

Follow the cell cycle; undergo mitosis; continue to proliferate throughout life; replace cells that are continuously being destroyed

Question 4

Quiescent Cells

Answer 4

Demonstrate a low level of replication; neither cycling nor dying, re-enter the cycle in reponnse to an appropriate stimulus; are in G0 and can be stimulated into G1

Question 5

Non-dividing or Permanent Cells

Answer 5

Have exited the cell cycle; cannot undergo mitotic division in postnatal life

Question 6

Adaptations: Physiologic vs. Pathologic

Answer 6

Physiologic adaptations: Responses of cells to normal stimulation by hormones or endogenous chemical mediators
Pathologic adaptations: responses to stress that all cells to modulate their structure and function and this escape injury

Question 7

Hypertrophy

Answer 7

An increase in the size of cells resulting in enlargement of organ size. Bigger cells no new cells and can be trigger by trophic hormones growth factors or mechanical stretch .
Occurs in cells incapable of dividing and has degenerative changes.

Question 8

Hyperplasia

Answer 8

An increase in the number of cells resulting in an increase in size or weight of an organ or tissue due to increased number of cells.
Occurs in cells capable of dividing and can have hormonal hyperplasia and compensatory hyperplasia.
Caused by excesses of hormones or growth factors acting on target cells.
Ex: Abnormal menstrual bleeding, benign prostatic hyperplasia, thyroid hyperplasia, hyperplasia of the endometrium

Question 9

Atrophy

Answer 9

Shrinkage in the size of the cell by loss of cell substance resulting in decreased protein synthesis and increased protein degradation. During early development embryonic structures undergo atrophy

Question 10

Atrophy: Pathologic

Answer 10

Common causes include:

1) Disuse atrophy
2) Denervation
3) Hypoperfusion: reduced blood supply
4) Inadequate Nutrition: protein calorie malnutrition

Question 11

Atrophy: Cell and Organ Effects

Answer 11

Degradation: Reduced tissue mass & function
Autophagy: self-eating starved cells eat their own components in an attempt to survive
Brown atrophy: Tissue discoloration from lysosomal accumulation of residual bodies
Decreased Hormonal Stimulation
Senile atrophy: Aging
Fibrotic Occlusion: secretory ducts
Pressure: Compression by a tumor

Question 12

Metaplasia

Answer 12

One cell type is replaced by another by reprogramming of stem cells

Question 13

Myeloid Metaplasia

Answer 13

Extramedullary Hematopoiesis: Proliferation of Hematopietic tissue in sites other than bone marrow such as spleen and liver

Question 14

Causes of Cellular Injury

Answer 14

Hypoxia: the most common cause of injury and occurs when lack of oxygen prevents the cell from synthesizing sufficient ATP by aerobic oxidation
Pathogens: can injure the body by direct infection of cells, production of toxins, or host inflammatory response

Question 15

What is the mechanism of cellular injury in hypoxia and ischemia?

Answer 15

Decrease intracellular generation of ATP which leads to failure of many energy-dependent cellular systems such as the ion pumps and depletion of glycogen stores

Question 16

Causes of Cellular Injury continued…

Answer 16

1) Immunologic reaction
2) Congenital disorders are inherited genetic mutations
3) Chemical injury can occur with drugs, poisons
4) Nutritional or vitamin imbalance
5) Physical forms of injury
6) Aging: alterations in replicative and repair abilities

Question 17

Mechanisms of Cellular Injury

Answer 17

1) Decreased ATP
2) Mitochondrial damage
3) Increased intracellular calcium
4) Increased free radicals
5) Increased cell membrane permeability

Question 18

Reversible vs. Irreversible Cell Injury

Answer 18

Reversible Cell Injury= decreased oxidative phosphorylation, ATP depletion, cellular swelling
Irreversible cell injury= cell lysis= cell death= mitochondrial irreversibility , membrane damage, lysosomal digestion,
nuclear degeneration

Question 19

Irreversible cell injury

Answer 19

1) Severe membrane damage: allows massive influx of calcium into the cell
2) Marked mitochondrial dysfunction: produces mitochondrial swelling
3) Rupture of the lysosomes: causes release of lysosomal digestive enzymes
4) Nuclear changes: can include pyknosis degeneration and condensation of nuclear chromatin

Question 20

Necrosis

Answer 20

Cell lysis, membrane pores, perforin-mediated cell killing.

Mechanisms of injury: ATP depletion, mitochondrial damage, calcium influx, oxidative stress

Question 21

Apoptosis: Cell death

Answer 21

Cell size: Shrunken reduced
Nucleus: Fragmentation into nucleosome-size fragments
Plasma membrane: Intact Altered structure & lipid orientation
Cellular contents: Intact, released apoptotic bodies
Inflammation: no
Role: Physiologic, pathologic

Question 22

Necrosis

Answer 22

Cell size: Swollen enlarged
Nucleus: Pyknosis, Karyorrhexis,
Plasma membrane: Dsirupted
Cellular contents: Enzymatic digestion, leakage out
Inflammation: Frequent
Role: Pathologic

Question 23

Cell Injury Phenomenon

Answer 23

Reversible
1) Cellular swelling: failure of ion pumps,
2) Fatty Change
Irreversible
1) Mitochondrial dysfunction cannot be corrected
2) Profound membrane function disturbances

Question 24

Mechanisms of Damage: Membrane permeability

Answer 24

1) Plasma membrane damage leads to loss of osmotic balance
2) Lysosomal membrane injury results in leakage of their enzymes into the cytoplasm and activation of the acid hydrolases in the acidic intracellular pH of the injured
3) Activation of lysosomes Ribonucleases, DNases, Proteases, Glucosidases, and other enzymes leads to enzymatic digestion of cell components, and cell death by necrosis

Question 25

Mitochondrial Pathway of Apoptosis

Answer 25

After cellular stress, the BCL-2 family of proteins is regulated by transcriptional and post-translational mechanisms

Question 26

Cytochrome C

Answer 26

Cytochrome c shuttles electrons between electron-chain complexes 3 and 4. If cytochrome c is not present electron flow stops and ATP synthesis does not occur.

Question 27

Anti-apoptotic

Answer 27

BCL2, BCL-XL, MCL1

Question 28

Pro-apoptotic

Answer 28

BAX, BAK

Question 29

Sensors

Answer 29

BAD, BIM, BID, Puma, Noxa

Question 30

BCL-2 Family Anti-apoptotic vs Pro-Apoptotic

Answer 30

Anti-apoptic members include: A1, BCL-2, BCL-w, BCL-xL, and MCL-1, all which contain four BCL-2 homology domains

Pro-apoptotic proteins are subdivided into effector and bh3-only members

Question 31

Autophagy: Survival Mechanism

Answer 31

Cellular stresses such as nutrient deprivation activate autophagy genes, which initiate the formation of membrane- bound vesicles . The starved cells lives by eating its own contents

Question 32

Cellular Aging

Answer 32

Progressive accumulation over the years of sub lethal injury that may lead to cell death or at least diminished capacity if the cell to respond to injury

Question 33

Morphologic changes associated with cell aging

Answer 33

Irregular nuclei, pleomorphic vacuolated mitochondria, dimished endoplasmic reticulum, distored golgi apparatus