cell injury & death

Question 1

mitochondrial damage following cell injury

Answer 1

mitochondrial damage => formation of mitochondrial transition pore => loss of mitochondrial membrane potential and function

apoptotic pathway = leakage of apoptotic proteins from mitochondria

necrotic pathway = decreased ATP production and increased ROS

Question 2

what kinds of molecular and biochemical changes occur as a result of cell injury?

Answer 2

• decreased ATP generation
• mitochondrial damage
• Ca2+ influx
• ROS accumulation
• membrane permeability
• DNA damage

Question 3

increased membrane permeability following cell injury

Answer 3

damage to cell/lysosomal/mitochondrial membranes from:

• ROS => lipid peroxidation
• hypoxia => decreased phospholipid synthesis
• increased cytosolic Ca => protease and phospholipase activation

Question 4

morphological changes in reversible cell injury visible (via light microscope and EM)

Answer 4

light:

• cell swelling
• eosinophilia
• cytoplasmic vacuoles

EM:

• cytoplasmic blebbing
• microvilli loss
• nuclear condensation
• mild mitochondrial swelling

Question 5

calcium influx following cell injury

Answer 5

increased cytosolic calcium from:

1) release from intracellular stores
2) influx across membranes

mitochondrial transition pore opens and enzymes (like ATPase) activate => less ATP

Question 6

when does cell injury occur?

Answer 6

when a cell’s ability to adapt to a stress is exceeded; can be reversible or irreversible

Question 7

gangrenous necrosis: cause and characteristics

Answer 7

cause: hypoxia/ischemia of the soft tissues of the lower limbs
characteristics: similar to coagulation necrosis

Question 8

abnormal intracellular depositions and calcifications in cell injury/death

Answer 8

• deposition of lipids (fatty liver)
• deposition of abnormal proteins
• lysosomal storage disease (endogenous materials)
• accumulation of indigestible (exogenous) materials

Question 9

fat necrosis: cause and characteristics

Answer 9

cause: alcohol/gall stones => hypersecretion => activated lipases generate FFA => saponification of FFA + Ca
characteristics: seen in pancreas, white chalky deposits

Question 10

cellular changes in necrosis

Answer 10

• cell swelling
• eosinophilia (due to RNA loss)
• glassy homogeneous pattern due to protein degradation
• loss of nuclear material: karyolysis (loss of basophilia with DNase activity), pyknosis (nuclear shrinkage), karyorrhexis (fragmentation)
• ghost like appearance
• inflammatory response to clean up

Question 11

morphological changes in irreversible cell injury visible (via light microscope and EM)

Answer 11

light:

• absent nuclei
• membrane disruption

EM:

• disrupted cell membranes
• swollen mitochondria
• electron dense deposits

Question 12

reperfusion injury

Answer 12

severe tissue damage following re-oxygenation after transient ischemia….burst of ROS => necrosis

Question 13

characteristics of irreversible cell injury

Answer 13

• mitochondrial swelling
• accumulations of dense inclusions in mitochondria
• nuclear changes
• rupture of lysosomes and membranes

Question 14

what kind of changes follow cell injury

Answer 14

molecular/biochemical => => => morphological

Question 15

intrinsic apoptotic pathway

Answer 15

aka mitochondrial pathway

1. cell injury
2. BCL2 signalling
3. mitochondrial destruction and release of pro-apoptotic proteins

Question 16

liquefactive necrosis: cause and characteristics

Answer 16

cause: brain ischemia
characteristics: liquefaction - cell outlines not intact and no nuclei visible

Question 17

accumulation of ROS following cell injury

Answer 17

produced by injurious stimuli and lead to:

• DNA damage/mutations
• lipid peroxidation and membrane damage
• protein modifications and misfolding

Question 18

fibrinoid necrosis: cause and characteristics

Answer 18

cause: immune reactions in blood vessels
characteristics: bright pink, amorphous appearance of vessel

Question 19

coagulative necrosis: cause and characteristics

Answer 19

cause: ischemia or exposure to toxic agents
characteristics: ghost cells - absent nuclei but outlines and cytoplasm still there

Question 20

what are some causes of cell injury?

Answer 20

• oxygen deprivation
• physical agents (trauma)
• chemical agents (toxins, drugs)
• infectious agents
• immune system
• genetic disease (polymorphism causing a different response to injury)
• nutritional abnormalities

Question 21

DNA damage following cell injury

Answer 21

DNA damage => triggering of death pathways

Question 22

extrinsic apoptotic pathway

Answer 22

aka death receptor pathway

1. receptor-ligand interactions
2. signalling pathway activates caspases

Question 23

how does hypoxia impact pH?

Answer 23

pH decrease due to:

• increased anaerobic glycolysis
• reduced glycogen
• increased lactic acid

Question 24

caseous necrosis: cause and characteristics

Answer 24

cause: tb
characteristics: granuloma forms with surrounding inflammatory cells

Question 25

characteristics of reversible cell injury

Answer 25

- ATP depletion - inhibited protein synthesis - loss of glycogen - subtle membrane failure => cell swelling

Question 26

key differences of necrosis vs apoptosis

Answer 26

necrosis: - death of groups of cells - always pathologic - causes inflammation - no energy required - random DNA degradation apoptosis: - death of single cells - physiologic or pathologic - no unregulated inflammation - requires energy (protein synthesis + de novo transcription) - nonrandom DNA fragmentation

Question 27

what happens when a cell does not have sufficient oxygen?

Answer 27

1. ***decreased generation of ATP*** by the ETC 2. failure of the Na+/K+ ATPase to maintain the membrane electrochemical gradient 3. increased intracellular Na+ leads to fluid entry and cell swelling separately, hypoxia => membrane damage

Question 28

cellular changes in apoptosis

Answer 28

- cell shrinkage - cytoplasmic blebbing - chromatin condensation - fragmentation of nucleus - caspase degradation of DNA into ladder - phagocytosis