Cell Injury & Necrosis

Question 1

What is cell injury?

Answer 1

Failure of cells to adapt to situation in order to maintain homeostasis

Question 2

What is hypoxia?

Answer 2

Deficiency of oxygen leading to impaired oxidative phosphorylation

Question 3

What are the causes of hypoxia?

Answer 3

Reduced blood supply or impaired venous drainage, reduced gas exchange, reduced oxygen carrying capacity of blood

Question 4

What are the 4 principle targets in cell injury?

Answer 4

mitochondrial damage, calcium homeostasis, damage to cell membrane, damage to DNA

Question 5

What are the effects of mitochondrial damage?

Answer 5

Decreased ATP, increased ROS

Question 6

What are the effects of ROS

Answer 6

Damage to cell wall, proteins and DNA

Question 7

What are the effects of calcium influx?

Answer 7

membrane damage, nuclear damage, further damage of mitochondria

Question 8

What defines irreversible cell injury?

Answer 8

uncorrectable mitochondrial dysfunction (therefore loss of ability to generate ATP) and loss of cell membrane integrity

Question 9

What is reversible cell injury?

Answer 9

Cell swelling due to failure of energy dependent pumps

Question 10

What is a Mallory-Denk body?

Answer 10

cell injury in the liver associated with alcohol poisoning

Question 11

What are the histology features of necrosis?

Answer 11

Increased cytoplasmic eosinophilia, karyolysis, pyknosis, karyorrhexis, and eventually a ghost outline of the cell

Question 12

What is karyolysis?

Answer 12

Decreased basophilia

Question 13

What is pyknosis?

Answer 13

nuclear shrinkage and increased basophilia

Question 14

What is karyorrhexis?

Answer 14

nuclear fragmentation

Question 15

What are the different patterns of tissue necrosis?

Answer 15

coagulative necrosis, caseous necrosis, liquefactive necrosis, fibrinoid necrosis, fat necrosis, necrosis in malignant neoplasms

Question 16

What is coagulative necrosis?

Answer 16

Typical of infarction in solid organs, slow enzymatic digestion where ghost outline is present for a few days, typically looks white/yellow

Question 17

What is caseous necrosis?

Answer 17

typically in TB, crumbly cheesy appearance, histologically - granular debris without cell borders

Question 18

What is liquefactive necrosis?

Answer 18

where enzymes digest dead cells very quickly and form a liquid mass - typical of cerebral infarction

Question 19

What is fat necrosis?

Answer 19

Destruction of fat because of release of lipase in acute pancreatitis, see chalky white deposits on omentum

Question 20

What is fibrinoid necrosis?

Answer 20

Usually seen in immune reactions involving blood vessels, intensely bright pink in H&E

Question 21

What are the microscopic features of apoptosis?

Answer 21

cell shrinkage, pink staining, no membrane failure, chromatin condenses, degradation, phagocytosed, little or no inflammation

Question 22

What are the two pathways of apoptosis?

Answer 22

Extrinsic (death receptor pathway) and Intrinsic (mitochondrial pathway)

Question 23

What is the intrinsic pathway of apoptosis?

Answer 23

Lack of survival signals lead to activation of BAX and BAK (pro-apoptotic proteins) which effect mitochondrial membrane causing it to leak cytochrome c and other pro-apoptotic proteins which leads to activation of initiator caspases which activates executioner caspases

Question 24

What is the extrinsic pathway of apoptosis?

Answer 24

Receptor ligand interactions between Fas ligands on T cells and TNF receptors causes activation of adapter proteins which activates initiator caspases and then executioner caspases

Question 25

What is alpha-1-antitrypsin deficiency?

Answer 25

A deficiency in an anti-protease enzyme which stops proteins from migrating from the ER to the golgi apparatus - leads to excessive deposition of abnormal protein in liver cells

Question 26

What is lipofuschin?

Answer 26

A yellow-brown pigment that normally accumulates with age - not pathological - accumulates in the brain, heart and lungs because of years of oxidative damage

Question 27

What is haemosiderin?

Answer 27

Large brown granules in a H&E stain or blue granules in a prussian blue stain - aggregates of ferritin micelles (iron) - pathological

Question 28

What are the two forms of pathological calcification?

Answer 28

dystrophic and metastatic - both are abnormal depositions of calcium salts

Question 29

What is dystrophic calcification?

Answer 29

occurs in degenerate or necrotic tissue

Question 30

What is metastatic calcification?

Answer 30

It is a result of high blood calcium levels