Cell injury Flashcards
What is the main difference between necrosis and apoptosis?
Necrosis- cell is killed externally. ALWAYS pathological. Often occurs with inflammation.
Apoptosis- Cell kills itself. Can be physiological or pathological. No inflammation.
What are some of the molecular/ biochemical mechanisms of necrosis?
- 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
What is the main cause of the depletion of ATP in necrosis?
Reduced supply of oxygen/ nutrients and increase of mitochondrial damage.
Has an affect on membrane transport, protein synthesis and lipogenesis
Describe the causes and consequences of mitochondrial damage in irreversible cell injury
Cause: hypoxia/ toxins
Effects: decreased ATP production/ release of proapoptotic proteins (cytochrome C)
Why might necrosis and apoptosis be connected?
Because the mitochondrial damage involved in necrosis causes proapoptotic proteins to be released too.
What are the causes and consequences of the influx of Ca and loss of Ca homeostasis in necrosis?
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)
What are the causes/ affects of accumulation of ROS during necrosis?
Causes: inflammation/ radiation/ chemicals/ reperfusion injury
Consequences: damage to lipids/ proteins and DNA
What is a free radical?
An unstable chemical that has a single unpaired electron i nits outer orbit- reacts with molecules nearby
Describe the causes and affects of defects in membrane permeability in necrosis (mitochondrial/ plasma and lysosomal membranes)
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
What are the nuclear changes that occur during necrosis?
- Karyolysis (nuclear fading)
- Pyknosis (nuclear shrinkage)
- Karyorrhexis (nuclear fragmentation)
Macroscopic morphologic alterations in necrosis involve the following tissue necrosis patterns…
Coagulative necrosis Liquefactive necrosis Gangrenous necrosis Caseous necrosis Fat necrosis
What is an infarct?
A localised area of coagulative necrosis caused by ischaemia due to vascular obstruction
What is a malacia?
Type of necrosis in the central nervous system
What is an abscess?
Encapsulated pus (collection of neutrophils and tissue debris)
What are the 3 types of gangrene?
Dry, moist and gas
What are the key points of apoptosis?
- 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
What are the causes of apoptosis?
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
What are the molecular/ biochemical mechanisms of apoptosis?
- Activation of caspases (enzymes involved in apoptosis)
- DNA and protein breakdown
- Membrane alteration and recognition by phagocytes
Why are caspases useful for determining apoptosis?
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.
What is the role of caspases?
Enzymes that cleave protein, they breakdown the cytoskeleton.
Caspases exist as inactive pro-enzymes and must undergo enzymatic cleavage to become active.
What are the major causes of DNA/ protein breakdown during apoptosis?
Drugs/ radiation/ oxidative stress/ inherited diseases
-DNA broken down by endonucleases which are inactivated by caspases/ protein broken down by caspases
What are the affects of membrane alterations in apoptosis?
Plasma membrane of apoptotic cells changes in ways that promote recognition of dead cells by phagocytes
What are the microscopic morphologic alterations that occur during apoptosis?
- Cell shrinkage
- Chromatin condensation
- Cytoplasmic blebs and apoptotic bodies
- Phagocytosis of apoptotic cells or cell bodies
Whats the difference between intrinsic and extrinsic apoptotic pathways?
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)
