Exam 2: Necrosis, Apoptosis, and Autolysis Flashcards

1
Q

What is necrosis?

A

Death of cells and tissues while the body is whole (still living)
Some cells and tissues are dead

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2
Q

What is necrobiosis?

A

The natural death of cells of tissues through aging, as distinguished from necrosis or pathological death

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3
Q

What are examples of necrobiosis?

A

Enterocytes forming crypts
Keratinocytes in the skin
These cells are constantly dying a being replaced

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4
Q

What is apoptosis?

A

Programmed cell death, requiring energy and certain enzymes

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5
Q

When is apoptosis commonly seen?

A

Following DNA damage

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6
Q

What is apoptosis a safeguard against?

A

Neoplasia following DNA damage

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7
Q

What happens during apoptosis?

A

The cell breaks up into small pieces surrounded by the cytoplasmic membrane

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8
Q

What is autolysis?

A

The destruction of tissues or cells of an organism by the action of substances, such as enzymes, that are produced within the organism
AKA self-digestion

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9
Q

When does death occur?

A

At the point at which a cell, even given proper substrates, can no longer resume the biochemical processes necessary for normal homeostasis

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10
Q

What are causes of cell death?

A
Loss of blood supply (ischemia)
Loss of nerve supply
Loss of endocrine stimulation
Endotoxins
Mechanical/thermal injury
Chemical injury
Pressure
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11
Q

What is seen grossly in the morphologic changes of cells as it dies?

A

Necrotic tissue tends to be lighter in color due to denaturing of proteins including cytochrome oxidases

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12
Q

What is seen histologically in the morphologic changes of cells as it dies?

A
Nuclear changes (pyknosis, karyorrhexis, karyolysis)
Cytoplasmic changes (increased eosinophilia, cytoplasmolysis, coagulation)
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13
Q

What is pyknosis?

A

Shrunken, dense nucleus

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14
Q

What is karyorrhexis?

A

Fragmentation of the nucleus

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15
Q

What is karyolysis?

A

Loss of the nucleus

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16
Q

What is cytoplasmolysis?

A

Cytoplasm broken up and gone

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17
Q

What is coagulation?

A

Cytoplasm denser and stains more pink than before

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18
Q

What are the types of necrosis?

A

Coagulative
Caseous
Liquefactive
Gangrenous

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19
Q

Describe coagulative necrosis

A

Complete loss of blood supply
Fat necrosis
Zenker’s necrosis

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20
Q

Describe caseous necrosis

A

Associated with granulomatous inflammation

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21
Q

Describe liquefactive necrosis

A

Enzymatic breakdown of tissue

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22
Q

Describe gangrenous necrosis

A

Archaic term applied to necrosis caused by loss of blood supply
Dry and wet gangrene

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23
Q

What happens as coagulative necrosis occurs?

A

Coagulation of proteins in the tissue

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24
Q

What are causes of coagulative necrosis?

A

Local heat
Local chemicals
Ischemia
Certain bacterial toxins

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25
What is the significance of coagulative necrosis?
Specific diagnostic lesion
26
What do you see grossly with coagulative necrosis?
Tissue retains original form and coherent strength Firm, pale, dry Will eventually become friable Often surrounded by a reddened area or hyperemia
27
What do you see microscopically with coagulative necrosis?
Tissue organization remains Cell outline remains with loss of cellular detail Nuclear changes Cytoplasmic coagulation and hypereosinophilia
28
What is the outcome of coagulative necrosis?
Removal through slow digestion Progression to liquefactive necrosis Mineralization Sequestration
29
What is Zenker's necrosis?
A type of coagulative necrosis is specific to striated muscle
30
What are causes of Zenker's necrosis?
Vitamin E deficiency Ischemic necrosis Certain bacterial toxins
31
What is seen grossly with Zenker's necrosis?
Original outline persists Muscle slightly swollen Waxy appearance Light in color
32
What is seen microscopically with Zenker's necrosis?
Preservation of tissue organization and cell outlines
33
What is fat necrosis?
Fat and glycerine combine with metallic ions to form soap (saponification)
34
What are the causes of fat necrosis?
Pancreatic fat necrosis Vitamin E deficiency Traumatic fat necrosis Metabolic fat necrosis
35
How does pancreatic fat necrosis occur?
Secondary to pancreatic disease with release of lipase and other enzymes that break down fat
36
How does vitamin E deficiency cause fat necrosis?
Manifested as steatitis leading to fat necrosis
37
How does traumatic fat necrosis occur?
Due to lying on a hard surface | Presents as firm tissue beneath the skin
38
How does metabolic fat necrosis occur?
Mesenteric and omental fat become firm around the viscera | Can cause obstructions
39
What is seen grossly with fat necrosis?
Loss of shine Dull, opaque Firm, soap-like consistency
40
What is seen microscopically with fat necrosis?
Cell outline remains | Cytoplasm replace by pale blue material (soap); solid to stippled
41
What is the outcome of fat necrosis?
Saponified fat remains in the abdominal cavity | It may have no effect or can cause mechanical effects
42
What are causes of caseous necrosis?
``` Bacterial infection Some chemicals (turpentine) ```
43
What is seen grossly with caseous necrosis?
Dry but slightly greasy Firm, but no cohesive strength, usually pale to white Easily separated with a blunt instrument
44
What is seen microscopically with caseous necrosis?
Loss of all tissue outline Amorphous, granular debris, mass Infiltrated with mΦ, multinucleated giant cells Often surrounded by fibrous connective tissue capsule
45
What is the outcome of caseous necrosis?
Encapsulation Liquefaction Mineralization
46
What are causes of liquefactive necrosis in the CNS?
Necrosis in the CNS almost always results in liquefactive necrosis (malacia) Low amounts of coagulative protein High amounts of lipids (tends to liquefy) Create a low pH
47
Describe liquefactive necrosis as an abscess
A liquid center A focus of liquefactive necrosis that is surrounded by a connective tissue capsule Bacteria and neutrophils release proteolytic enzymes that liquefy tissue
48
What is seen grossly with liquefactive necrosis?
A fluid filled cavity in a tissue White to pale tan, brown, red, green liquid Consistency of cream or pudding Frequently more foul smelling than coagulative or caseous necrosis Frequently surrounded by fibrous conenctive tissue capsule
49
What is seen microscopically liquefactive necrosis?
Pink, proteinacious fluid | Edges made up of frayed tissue
50
What is the outcome of liquefactive necrosis?
Walled off Remain as fluid Resorbed Replaced by scar tissue
51
What is gangrenous necrosis?
Necrotic tissue invaded by saprophytic bacteria
52
What are causes of moist gangrene?
Twisted intestine; devitalized intestine Lung due to aspiration Anywhere else conditions are right
53
What is seen grossly with moist gangrene?
Swollen, soft, pulpy, dark in color with putrefactive smell | In vivo- insensitive; cold
54
What are causes of dry gangrene?
Seen in extremities due to vascular compromise or ischemia; ergot Not as many bacteria proliferating
55
What is seen grossly dry gangrene?
Tissue is shrunken, wrinkled, leathery, often firm Can be pale or darker than normal Marginal hyperemia
56
What are results of necrosis?
``` Consequences if the animal survives Calcification of dead tissue Liquefaction and removal Liquefaction and encapsulation Replacement with fibrous connective tissue Liquefaction and migration Desquamation ```
57
What are the consequences of necrosis if the animal survives?
Organ dysfunction Necrotic tissue removed Defect filled by fibrous connective tissue
58
Describe calcification of dead tissue
A way to neutralize the effects of necrotic tissue Can have mechanical effects depending on where Dystrophic mineralization
59
Describe liquefaction and removal
Slow and imperceptible | Removed by mΦ and lymph drainage
60
Describe liquefaction and migration
Migration of liquid along any plane of least resistance | Pressure builds up due to influx of cells, which causes migration
61
Describe encapsulation with sequestration
Isolation by encapsulation | Commonly seen with necrosis of bone
62
What is desquamation?
Shedding of dead tissue from a surface
63
What are types of desquamation?
Erosion Ulceration Slough
64
What is erosion?
Loss of epithelium with an intact basement membrane
65
How does erosion heal?
Cells will regenerate with an intact basement membrane | Heals by regeneration (no scar)
66
What is ulceration?
Destruction of the basement membrane
67
How does ulceration heal?
Always heals by scarring (connective tissue)
68
What is slough?
Shedding of a large amount of tissue (second and third degree burns)
69
What does necrosis occur in the absence of?
Energy. It does not require metabolism to complete
70
What is the mechanism of necrosis?
Mitochondrial ATP production stops Plasma membrane energy-dependent Na pumps shut down Na/H2O enter cell Cell swelling/membrane stretching Glycolysis allows cell to function at a decreased level Failure of Ca pumps--- Ca enters the cell--- many effects Ca activation of enzyme systems Unfolded protein response (attempt to prevent protein denaturation) Protein denaturation starts Damage to all membranes of all organelles ER and other organelles swell More changes in membrane permeability with massive influx of Ca
71
What are results of the mechanisms of necrosis?
Mitochondria are often damaged Inner membrane permeability is increased Loss of proton motive force leads to deathblow for the cells Leakage of cytochrome c
72
What is apoptosis?
Programmed cell death
73
What happens during apoptosis?
``` Deletion of un-needed cells during embryogenesis Normal involution Regression of hyperplasia Deletion of genetically unstable cells Activation of viruses Activation by immune cells ```
74
Does apoptosis elicit inflammation?
No
75
What does apoptosis require?
Energy
76
What is apoptosis mediated by?
Caspases
77
At what level does apoptosis act?
The individual cell level
78
What are features of apoptosis?
Cells shrink, round up, become more dense, and detach from neighbors Chromatin becomes very dense and separates into homogeneous, frequently semi-lunar or sickle shaped mass adjacent to the nuclear membrane Budding and blebbing Phagocytosis by macrophages and surrounding cells Characteristic DNA ladder formation
79
Is death by apoptosis normal?
Yes, it serves to eliminate cells that are no longer needed
80
What are physiologic situations where apoptosis occurs?
``` Embryogenesis Hormone dependent involution Cell deletion in proliferating pools Death of senile cells (neutrophils) Elimination of self reactive lymphocytes Cells death induced by cytotoxic T cells ```
81
What are events that are caused by hormone dependent involution?
Post partum endometrial cell breakdown Regression of the lactating mammary glands after weaning Prostatic atrophy castration
82
What are pathologic situations where apoptosis occurs?
Cell death following injury Cell injury in some viral diseases Pathogenic atrophy in some organs Cell death in some tumors
83
What are biochemical features of apoptosis?
Apoptotic cells usually exhibit a distinctive constellation of biochemical modifications that underlie the structural changes in cells Protein cleavage DNA breakdown Phagocytic recognition
84
How does protein cleavage occur?
Via activation of several members of a cysteine protease family called caspases
85
What are the mechanisms of apoptosis?
Extrinsic (death receptor-initiated pathway) Intrinsic (mitochondrial pathway) Cytotoxic T cell method
86
What is the extrinsic pathway of apoptosis initiated by?
Engagement of cell surface death receptors
87
What is the intrinsic pathway of apoptosis a result of?
Increased mitochondrial permeability and release of pro-apoptotic molecules into the cytoplasm
88
Read about the extrinsic and intrinsic pathways of apoptosis
Read about the extrinsic and intrinsic pathways of apoptosis
89
Describe the cytotoxic T cell method
Cytotoxic t lymphocytes recognize foreign Ag present on infected cell membranes On recognition, CTLs release perforins Granzyme B cleaves proteins at aspartate residues and activates several caspases
90
What is the cytotoxic T cell method used as?
A bypass mechanism for cells that refuse suicide via extrinsic or intrinsic pathways
91
Describe somatic death
Like cell death, often difficult to pinpoint the exact time In humans, considered to be cessation of EEG activity Not all tissues die at the same time
92
How long can neurons survive?
3 minutes
93
How long can cardiac muscle survive?
20 minutes
94
How long can parenchymal cells survive?
1 hour
95
How long can chondrocytes survive?
Several days