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Flashcards in Cell injury Deck (24)
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1
Q

What is the main difference between necrosis and apoptosis?

A

Necrosis- cell is killed externally. ALWAYS pathological. Often occurs with inflammation.
Apoptosis- Cell kills itself. Can be physiological or pathological. No inflammation.

2
Q

What are some of the molecular/ biochemical mechanisms of necrosis?

A
  • Depletion of ATP
  • Influx of calcium/ loss of calcium homeostasis
  • Changes in membrane permeability
  • Accumulation of oxygen derived free radicals
  • Damage to DNA and proteins
3
Q

What is the main cause of the depletion of ATP in necrosis?

A

Reduced supply of oxygen/ nutrients and increase of mitochondrial damage.
Has an affect on membrane transport, protein synthesis and lipogenesis

4
Q

Describe the causes and consequences of mitochondrial damage in irreversible cell injury

A

Cause: hypoxia/ toxins
Effects: decreased ATP production/ release of proapoptotic proteins (cytochrome C)

5
Q

Why might necrosis and apoptosis be connected?

A

Because the mitochondrial damage involved in necrosis causes proapoptotic proteins to be released too.

6
Q

What are the causes and consequences of the influx of Ca and loss of Ca homeostasis in necrosis?

A

Cause: Ischemia/ toxins
Consequences: increased mitochondrial permeability/ activation of multiple cellular enzymes (phospholipids/ proteases/ endonucleasaes/ ATPases) (a lot of intracellular Ca is sequestered in the mitochondria)

7
Q

What are the causes/ affects of accumulation of ROS during necrosis?

A

Causes: inflammation/ radiation/ chemicals/ reperfusion injury
Consequences: damage to lipids/ proteins and DNA

8
Q

What is a free radical?

A

An unstable chemical that has a single unpaired electron i nits outer orbit- reacts with molecules nearby

9
Q

Describe the causes and affects of defects in membrane permeability in necrosis (mitochondrial/ plasma and lysosomal membranes)

A

Cause: ischemia, toxins, viruses, physical/ chemical agents
Affects: mitochondrial membrane- decreased ATP production, apoptosis
Plasma membrane- loss of cellular contents and osmotic balance
Lysosomal membranes- leakage of enzymes( enzymatic digestion of proteins, DNA/RNA, glycogen

10
Q

What are the nuclear changes that occur during necrosis?

A
  • Karyolysis (nuclear fading)
  • Pyknosis (nuclear shrinkage)
  • Karyorrhexis (nuclear fragmentation)
11
Q

Macroscopic morphologic alterations in necrosis involve the following tissue necrosis patterns…

A
Coagulative necrosis
Liquefactive necrosis 
Gangrenous necrosis 
Caseous necrosis
Fat necrosis
12
Q

What is an infarct?

A

A localised area of coagulative necrosis caused by ischaemia due to vascular obstruction

13
Q

What is a malacia?

A

Type of necrosis in the central nervous system

14
Q

What is an abscess?

A

Encapsulated pus (collection of neutrophils and tissue debris)

15
Q

What are the 3 types of gangrene?

A

Dry, moist and gas

16
Q

What are the key points of apoptosis?

A
  • Tightly regulated cell suicide program
  • Apoptotic cell break up into fragments (apoptotic bodies) with intact plasma membrane (no leakage so NO INFLAMMATION)
  • Apoptotic bodies removed by phagocytes
17
Q

What are the causes of apoptosis?

A

Can be either physiologic or pathologic.

Physiologic: programmed cell death. Can occur during embryogenesis, cell loss in proliferating cell populations, elimination of cell reactive lymphocytes, leukocytes after inflammatory response

Pathologic: DNA damage, accumulation of misfolded proteins, certain viral infections

18
Q

What are the molecular/ biochemical mechanisms of apoptosis?

A
  • Activation of caspases (enzymes involved in apoptosis)
  • DNA and protein breakdown
  • Membrane alteration and recognition by phagocytes
19
Q

Why are caspases useful for determining apoptosis?

A

Because the enzymes are pretty unique to apoptosis so identification of them in labs allows you to be sure if it apoptosis not necrosis occurring.

20
Q

What is the role of caspases?

A

Enzymes that cleave protein, they breakdown the cytoskeleton.
Caspases exist as inactive pro-enzymes and must undergo enzymatic cleavage to become active.

21
Q

What are the major causes of DNA/ protein breakdown during apoptosis?

A

Drugs/ radiation/ oxidative stress/ inherited diseases

-DNA broken down by endonucleases which are inactivated by caspases/ protein broken down by caspases

22
Q

What are the affects of membrane alterations in apoptosis?

A

Plasma membrane of apoptotic cells changes in ways that promote recognition of dead cells by phagocytes

23
Q

What are the microscopic morphologic alterations that occur during apoptosis?

A
  • Cell shrinkage
  • Chromatin condensation
  • Cytoplasmic blebs and apoptotic bodies
  • Phagocytosis of apoptotic cells or cell bodies
24
Q

Whats the difference between intrinsic and extrinsic apoptotic pathways?

A

Intrinsic: major mechanism. Result of increased mitochondiral permeability causing the release of proapoptotic proteins (cytochrome C)

Extrinsic: initiated by engaement of plasma membrane death receptors (can be by cytotoxic T cells)