Cell Injury & Necrosis Flashcards
What is cell injury?
Failure of cells to adapt to situation in order to maintain homeostasis
What is hypoxia?
Deficiency of oxygen leading to impaired oxidative phosphorylation
What are the causes of hypoxia?
Reduced blood supply or impaired venous drainage, reduced gas exchange, reduced oxygen carrying capacity of blood
What are the 4 principle targets in cell injury?
mitochondrial damage, calcium homeostasis, damage to cell membrane, damage to DNA
What are the effects of mitochondrial damage?
Decreased ATP, increased ROS
What are the effects of ROS
Damage to cell wall, proteins and DNA
What are the effects of calcium influx?
membrane damage, nuclear damage, further damage of mitochondria
What defines irreversible cell injury?
uncorrectable mitochondrial dysfunction (therefore loss of ability to generate ATP) and loss of cell membrane integrity
What is reversible cell injury?
Cell swelling due to failure of energy dependent pumps
What is a Mallory-Denk body?
cell injury in the liver associated with alcohol poisoning
What are the histology features of necrosis?
Increased cytoplasmic eosinophilia, karyolysis, pyknosis, karyorrhexis, and eventually a ghost outline of the cell
What is karyolysis?
Decreased basophilia
What is pyknosis?
nuclear shrinkage and increased basophilia
What is karyorrhexis?
nuclear fragmentation
What are the different patterns of tissue necrosis?
coagulative necrosis, caseous necrosis, liquefactive necrosis, fibrinoid necrosis, fat necrosis, necrosis in malignant neoplasms
What is coagulative necrosis?
Typical of infarction in solid organs, slow enzymatic digestion where ghost outline is present for a few days, typically looks white/yellow
What is caseous necrosis?
typically in TB, crumbly cheesy appearance, histologically - granular debris without cell borders
What is liquefactive necrosis?
where enzymes digest dead cells very quickly and form a liquid mass - typical of cerebral infarction
What is fat necrosis?
Destruction of fat because of release of lipase in acute pancreatitis, see chalky white deposits on omentum
What is fibrinoid necrosis?
Usually seen in immune reactions involving blood vessels, intensely bright pink in H&E
What are the microscopic features of apoptosis?
cell shrinkage, pink staining, no membrane failure, chromatin condenses, degradation, phagocytosed, little or no inflammation
What are the two pathways of apoptosis?
Extrinsic (death receptor pathway) and Intrinsic (mitochondrial pathway)
What is the intrinsic pathway of apoptosis?
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
What is the extrinsic pathway of apoptosis?
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
What is alpha-1-antitrypsin deficiency?
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
What is lipofuschin?
A yellow-brown pigment that normally accumulates with age - not pathological - accumulates in the brain, heart and lungs because of years of oxidative damage
What is haemosiderin?
Large brown granules in a H&E stain or blue granules in a prussian blue stain - aggregates of ferritin micelles (iron) - pathological
What are the two forms of pathological calcification?
dystrophic and metastatic - both are abnormal depositions of calcium salts
What is dystrophic calcification?
occurs in degenerate or necrotic tissue
What is metastatic calcification?
It is a result of high blood calcium levels
