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

22
Q

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

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
Assessment of Necrosis Morphilogical Discontinuous plasma & organelle membranes
TEM
26
Assessment of Necrosis Biochemical
Random DNA degradation Increased levels of lactate dehydrogenase
27
Necrosis of the kidney
28
Apoptosis
29
Steps of apoptosis Intracellular
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
Steps of apoptosis Extracellular
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
Webbing of human toes may occur due to…
…interruption of apoptosis
32
Abnormal tissue homeostasis Loss of cells due to apoptosis
Immune deficiency syndromes, some types of anemia
33
Abnormal tissue homeostasis Irreplaceable due to non-renewing cell populations (brain or heart)
Alzheimer’s, Parkinsons, myocardial infarction
34
Abnormal tissue homeostasis Accumulation of cells due to failure of apoptosis
Malignant neoplasia, autoimmune syndromes
35
Two mechanisms of apoptosis
Intrinsic (mitochondrial) Extrinsic (Death receptor) Differ in induction and regulation Both result in activation of initiator & executioner caspases
36
Intrinsic B C A 9 C 3
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
Extrinsic F FT D C83
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
Bcl-2 Protein Family Two functional classes
Pro-Apoptotic Anti-Apoptotic
39
Bcl-2 protein family Pro-apoptotic
Bid (Links extrinsic & intrinsic pathways Bax & Bak (permeabilization of mitochondrial outer membrane)
40
Bcl-2 Protein Family Anti-apoptotic
Bcl-2 Bcl-xL
41
Assessment of Apoptosis
Caspase Activity
42
Assessment of Apoptosis Annexin 5
Protein binds to phosphotidylserine when exposed on the outer leaflet of plasma membrane.
43
Assessment of Apoptosis DNA Laddering
DNAse cleaves intermucleosomal DNA 180-200 bp fragments
44
Assessment of Apoptosis TUNEL
Terminal Uridine deoxyNucleotidyl transferase nick End Labeling Detects DNA fragmentation
45
DNA Laddering
Agrose gel electrophoresis of DNA from cultured cells A. Viable cells B. Apoptotic Cells C. Necrotic Cells
46
TUNEL
Assay detects DNA fragmentation Tagged or labeled deoxynucleotides to 3’ DNA ends
47
TUNEL
Assay detects DNA fragmentation Tagged or labeled deoxynucleotides to 3’ DNA ends