24. Apoptosis And Necrosis Flashcards

1
Q

Increased in muscle size

A

Hypertrophy

Can act as a way for muscle cell to adapt to increase workload.

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2
Q

Two types of cellular response to stress and injury

A

Physiological
Pathological

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3
Q

Adaptation to a stimulus within the normal range

A

Physiological Response

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4
Q

Adaptation to a stimulus outside the normal physiological range
May result in cellular malfunction, damage, or death

A

Pathological Response

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5
Q

Fate of the cell exposed to a stimulus depends on:

A

Type of stimulus
Duration
Magnitude
Vulnerability of cell

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6
Q

Common causes of Cell injury
Metabolic

A

Oxygen deprivation
Hypoxia: oxygen deficiency
Ischemia: Blood flow deficiency

Nutritional
Deficiency, excess

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7
Q

Common causes of Cell injury
Chemical

A

Drugs, alcohol, poisons

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8
Q

Common causes of Cell injury
Physical

A

Trauma, extreme temperatures, radiation

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9
Q

Common causes of Cell injury
Biological

A

Virus, bacteria, parasite

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10
Q

Common causes of Cell injury
Immunological

A

Allergic reactions, autoimmune disease

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11
Q

Common causes of Cell injury
Genetic

A

Chromosomal abnormalities
Mutations

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12
Q

Common causes of Cell injury
Aging

A

Cellular senescence

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13
Q

Common causes of cell injury
Four major intracellular systems affected

A
  1. Membrane integrity (cellular plasma membrane, organelle membranes)
  2. ATP production
  3. Protein synthesis
  4. Genomic or chromosomal integrity
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14
Q

Early cellular responses to injury
Earliest evidence to injury
Loss of normal staining intensity due to swelling of organelles

A

Cloudy swelling

Rough Endoplasmic Reticulum becomes dilated with the loss of surface ribosomes.
Loss of cytoplasmic free ribosomes.

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15
Q

Early Cellular Responses to injury
Continued swelling of organelles
Vacuoles appear in cytoplasm (stains faintly with loss of basophilia)

A

Hydropic degeneration

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16
Q

Early cellular response to injury
Accumulation of triglycerides in cytoplasm
Most common in liver (rarely in skeletal muscle
Common causes (toxins, alcohol, chronic hypoxia)

A

Fatty change (steatosis)

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17
Q

Cell accumulation disorders (CLeG V)

A

CLeG V
Cancer
Lupus erythematosus
Glomerulonephritis
Viral infections

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18
Q

Cell Loss disorders (MAAAP)

A

MAAAP
Myocardial infarction
Alzheimers
AIDS
Aplastic anemia
Parkinson’s

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19
Q

Cell death
Cell swelling, damage to plasma membrane, random DNA degradation

A

Necrosis
Principle outcome in many injuries (ex. Ishemia, toxins, infections & trauma)

20
Q

Cell death
Cell shrinkage, plasma membrane blebbing, aggregation of chromatin, fragmentation of nucleus, oligonucleosomal DNA fragmentation, caspase cascade activation

A

Apoptosis
Regulated cell suicide program
Occurs during development and throughout adulthood
Physiological (development, tissue homeostasis)
Some pathological (DNA damage, misfolded proteins, viral infections)

21
Q

Pathological, acute cell injury, cell unable to maintain homeostasis, cell swelling, loss of plasma membrane integrity, cell contents released, surrounding tissue damage, inflammation

A

Necrosis

22
Q

Physiological (planned), genetic, programmed cell death, cell shrinking, DNA aggregation, maintains plasma membrane integrity, no surrounding tissue damage, no inflammation

A

Apoptosis

23
Q

Assessment of Necrosis
Morphilogical
Live cell imaging
Intercalates & labels DNA
If positive=leaky/discontinuous plasma membrane =necrosis

A

Propidium Iodide (PI) staining

24
Q

Assessment of Necrosis
Morphilogical
Increased eosinophilia (loss of cytoplasmic RNA, increase in denatured proteins)
Variable nuclear staining (typical loss of basophilia & total loss of nuclear staining after a couple days; sometimes pyknosis visible)

A

H&E staining

25
Q

Assessment of Necrosis
Morphilogical
Discontinuous plasma & organelle membranes

A

TEM

26
Q

Assessment of Necrosis
Biochemical

A

Random DNA degradation

Increased levels of lactate dehydrogenase

27
Q

Necrosis of the kidney

A
28
Q

Apoptosis

A
29
Q

Steps of apoptosis
Intracellular

A
  1. Phosphotidylserine moves from inner to outer leaflet
  2. Membranes bleb
  3. Condensed chromatin is found in nucleus.
  4. Cytochrome C is released from the mitochondria
30
Q

Steps of apoptosis
Extracellular

A
  1. Phosphotidylserine is exposed on the surface of apoptotic cells
  2. The apoptotic cell is engulfed or phagocytosed by a macrophage
  3. The engulfed apoptotic cells is internalized then degraded within the macrophage
  4. The macrophage releases cytokines IL-10 and TGF-beta to inhibit inflammation.
31
Q

Webbing of human toes may occur due to…

A

…interruption of apoptosis

32
Q

Abnormal tissue homeostasis
Loss of cells due to apoptosis

A

Immune deficiency syndromes, some types of anemia

33
Q

Abnormal tissue homeostasis
Irreplaceable due to non-renewing cell populations (brain or heart)

A

Alzheimer’s, Parkinsons, myocardial infarction

34
Q

Abnormal tissue homeostasis
Accumulation of cells due to failure of apoptosis

A

Malignant neoplasia, autoimmune syndromes

35
Q

Two mechanisms of apoptosis

A

Intrinsic (mitochondrial)
Extrinsic (Death receptor)

Differ in induction and regulation

Both result in activation of initiator & executioner caspases

36
Q

Intrinsic B C A 9 C 3

A

Death signal (DNA damage) —> BAX (pro-apoptotic protein upregulated) —> Release of Cytochrome C from Mitochondria —> Activates Apaf-1 (assembly of Apoptosome) —> Activates Procaspase 9 (initiator) —> Activation of the Caspase cascade —> Activates Caspase 3 (activator).

BCA9C3

37
Q

Extrinsic F FT D C83

A

Fas ligand (binding of ligand to death receptor) —> FADD & TRADD (recruitment of death adaptor proteins) —> DISC formed (death inducing signaling complex) —> Caspase Cascade —> Caspase 8 (initiator) —> Caspase 3 (effector caspase).

38
Q

Bcl-2 Protein Family
Two functional classes

A

Pro-Apoptotic
Anti-Apoptotic

39
Q

Bcl-2 protein family
Pro-apoptotic

A

Bid (Links extrinsic & intrinsic pathways

Bax & Bak (permeabilization of mitochondrial outer membrane)

40
Q

Bcl-2 Protein Family
Anti-apoptotic

A

Bcl-2
Bcl-xL

41
Q

Assessment of Apoptosis

A

Caspase Activity

42
Q

Assessment of Apoptosis
Annexin 5

A

Protein binds to phosphotidylserine when exposed on the outer leaflet of plasma membrane.

43
Q

Assessment of Apoptosis
DNA Laddering

A

DNAse cleaves intermucleosomal DNA
180-200 bp fragments

44
Q

Assessment of Apoptosis
TUNEL

A

Terminal Uridine deoxyNucleotidyl transferase nick End Labeling

Detects DNA fragmentation

45
Q

DNA Laddering

A

Agrose gel electrophoresis of DNA from cultured cells
A. Viable cells
B. Apoptotic Cells
C. Necrotic Cells

46
Q

TUNEL

A

Assay detects DNA fragmentation
Tagged or labeled deoxynucleotides to 3’ DNA ends

47
Q

TUNEL

A

Assay detects DNA fragmentation
Tagged or labeled deoxynucleotides to 3’ DNA ends