Cell injury

Question 1

What is the main difference between necrosis and apoptosis?

Answer 1

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

Question 2

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

Answer 2

• 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

Question 3

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

Answer 3

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

Question 4

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

Answer 4

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

Question 5

Why might necrosis and apoptosis be connected?

Answer 5

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

Question 6

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

Answer 6

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)

Question 7

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

Answer 7

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

Question 8

What is a free radical?

Answer 8

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

Question 9

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

Answer 9

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

Question 10

What are the nuclear changes that occur during necrosis?

Answer 10

• Karyolysis (nuclear fading)
• Pyknosis (nuclear shrinkage)
• Karyorrhexis (nuclear fragmentation)

Question 11

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

Answer 11

Coagulative necrosis
Liquefactive necrosis 
Gangrenous necrosis 
Caseous necrosis
Fat necrosis

Question 12

What is an infarct?

Answer 12

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

Question 13

What is a malacia?

Answer 13

Type of necrosis in the central nervous system

Question 14

What is an abscess?

Answer 14

Encapsulated pus (collection of neutrophils and tissue debris)

Question 15

What are the 3 types of gangrene?

Answer 15

Dry, moist and gas

Question 16

What are the key points of apoptosis?

Answer 16

• 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

Question 17

What are the causes of apoptosis?

Answer 17

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

Question 18

What are the molecular/ biochemical mechanisms of apoptosis?

Answer 18

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

Question 19

Why are caspases useful for determining apoptosis?

Answer 19

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.

Question 20

What is the role of caspases?

Answer 20

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

Question 21

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

Answer 21

Drugs/ radiation/ oxidative stress/ inherited diseases

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

Question 22

What are the affects of membrane alterations in apoptosis?

Answer 22

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

Question 23

What are the microscopic morphologic alterations that occur during apoptosis?

Answer 23

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

Question 24

Whats the difference between intrinsic and extrinsic apoptotic pathways?

Answer 24

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)