Necrosis & Apoptosis Flashcards

1
Q

What is the definition of necrosis?

A

Focal death of cells with degradation of tissue by hydrolytic enzymes liberated by cells. It is invariably (always) accompanied by inflammatory reaction.

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2
Q

What are the causes of necrosis?

A

Hypoxia, chemical, physical agents, microbial agents & immunologic injury

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3
Q

2 essential changes bring about irreversible cell injury in necrosis

A
  1. Cell digestion by lytic enzymes

2. Denaturation of proteins

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4
Q

What are the morphological changes in necrosis?

A
  1. Cytoplasmic changes
    - increased eosinophilia (more red)
    Due to:
    -loss of cytoplasmic RNA
    -denatured cytoplasmic protein
    -more glassy homogenous appearance (due to loss of glycogen)
    -cytoplasm becomes vacuolated & moth-eaten when cytoplasmic organelles are digested by enzymes
    -occasionally show dystrophic calcification
  2. Nuclear changes
    - due to non-specific breakdown of DNA
    - can occur karyolysis (nuclear fading) OR pyknosis (nuclear shrinkage) OR karyorrhexis (nuclear fragmentation)
    - nuclear will undergo dissolution which leads to anuclear necrotic cell
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5
Q

6 types of necrosis are….

A
  1. Coagulative necrosis (most common)
  2. Liquefactive necrosis
  3. Gangrenous necrosis
  4. Caseous necrosis
  5. Fat necrosis
  6. Fibrinoid necrosis
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6
Q

What are the causes of coagulative necrosis?

A

Mostly from sudden ischaemia, less often from bacteria & chemical agents

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7
Q

What are the common organs affected by coagulative necrosis?

A

Heart
Kidney
Spleen

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8
Q

Describe the gross appearance of coagulative necrosis

A

Early stage : pale, firm, slightly swollen

Later stage : yellowish, softer & shrunken

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9
Q

Describe the microscopic appearance of coagulative necrosis

A
  • outlines of cells only can be seen but the nuclear and cytoplasmic detail are lost
  • swollen
  • more eosinophilic
  • inflammatory cell present
  • dead cells are phagocytosed
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10
Q

What is the cause of liquefactive necrosis

A

Ischaemic injury

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11
Q

What is the characteristic feature of liquefactive necrosis

A

Liquid viscous mass due to digestion of the dead cells

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12
Q

Describe the gross appearance of liquefactive necrosis

A
  • affected area is soft with liquefied center containing necrotic debris
  • later, a cyst wall is formed
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13
Q

Describe the microscopic appearance of liquefactive necrosis

A
  • cystic space contains necrotic debris & macrophages
  • cyst wall formed by proliferating capillaries, inflammatory cells & gliosis (in brain) & fibroblast (in abscess cavity).
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14
Q

What is the cause of wet gangrene?

A
  • due to superimposed bacterial infection
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15
Q

What is the most often effect (infection) that is caused by caseous necrosis

A

Tuberculous infection

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16
Q

Describe the gross appearance of caseous necrosis

A
  • resemble dry cheese

- soft, granular & yellowish

17
Q

Describe the microscopic appearance of caseous necrosis

A
  • collection of lysed/fragmented cells

- amorphous (shapeless) granuloma

18
Q

What is fat necrosis?

A

It is a special form of cell death following acute pancreatic necrosis & traumatic fat necrosis (in breast).

Occur in organs with fat

19
Q

Describe the gross appearance of fat necrosis

A

Appears as yellowish white firm deposit

20
Q

Describe the microscopic appearance of fat necrosis

A
  • shadowy outlines of necrotic fat cell

- surrounded by inflammatory reaction

21
Q

What is fibrinoid necrosis?

A

Special form of necrosis usually seen in immune reaction involving blood vessels.

22
Q

What causes fibrinoid necrosis

A

Occurs when antigen-antibody complexes deposited in the arterial wall

23
Q

What causes the bright pink & amorphous appearance in fibrinoid necrosis H&E stain

A

Immune complexes together with fibrin (leaks from vessels)

24
Q

What is the definition of apoptosis

A

Pathway of cell death induced by tight regulated suicide program (program cell death).

Enzymes will degrade the cell’s own nuclear DNA & nuclear & cytoplasmic proteins.

25
Q

What are the morphological changes in apoptosis?

A
  • cell shrinkage (due to cytoplasm dense & organelles more tightly packed)
  • chromatin condensation (most characteristic feature)
  • formation of cytoplasmic blebs & apoptotic bodies
  • phagocytosis of apoptotic bodies by macrophages (usually)
26
Q

Biochemical features of apoptosis

A
  1. Activation of caspases
    - to activate DNAases to break down nuclear DNA
  2. DNA & protein breakdown
  3. Membrane alteration & recognition of apoptotic cells by phagocytes
27
Q

What are the 3 mechanisms of apoptosis

A
  1. Initiation phase
    - caspases become catalytically active
    - occurs by 2 signals from intrinsic & extrinsic pathway
  2. Execution phase
    - other caspases trigger the degradation of critical cellular component
    - fragmentation of nuclei
  3. Removal of dead cells
    - formation of apoptotic bodies breaks cells up into fragments that are edible for phagocytes
    - cells that are dying by apoptosis secrete soluble factors that recruit phagocytes
28
Q

What are the two different pathways of apoptosis?

A
  1. Intrinsic (mitochondrial) pathway

2. Extrinsic (death receptor-initiated) pathway (FAS, TNF receptor)

29
Q

What happens when apoptosis is dyrsregulated?

A
  • if apoptosis rate is low : may prolong survival of abnormal cells
  • if apoptosis rate is excessive : cause marked loss of normal cells
30
Q

What are the effects of accumulation of abnormal cells?

A

Cancers: especially tumours with p53 mutation

Autoimmune disorder: which could arise if autoreactive lymphocytes are not eliminated

31
Q

What are some of the disorders of increased apoptosis & excessive cell death?

A
  1. Neurogenerative disease (loss of specific sets of neurons0
    - e.g. spinal muscular atrophies
  2. Ischaemic injury
    - e.g. myocardial infarction, stroke
  3. Death of virus infected cells