Cell Death, Injury, And Adaptations. Flashcards
Ischemia
Lack of blood flow. Common cause of hypoxia.
Hypoxia
Oxygen deficiency.
Reversible injury
Stage of cell injury at which the cell can return to normal function, if the damaging stimulus is removed.
Cellular swelling
Commonly seen in cell injury associated with increased permeability of the plasma membrane. Also called hydropic change and vaculolar degeneration.
Fatty change
Appearance of triglyceride containing lipid vacuoles in the cytoplasm. Common in liver.
Causes of cell death
- inability to restore mitochondrial function
- loss of structure or function of plasma membrane or intracellular membranes.
- Loss of DNA integrity
Necrosis
uncontrolled, “accidental” cell death. Usually involves leakage of lysosomes into the cytoplasm.
Apoptosis
Controlled cell death. Cells condense and form membrane blebs, chromatin condenses. Phagocytes then consume the cells.
Pyknosis
Nuclear shrinkage and increased basophilia. DNA becomes a dark, shrunken mass.
Karyorrhexis
Pyknotic nucleus undergoes fragmentation.
Karyolysis
The nucleus is digested by DNase activity.
Coagulative necrosis
The underlying tissue architecture is preserved for at least several days. Tissue has a firm texture. Proteolysis of the dead cells is blocked. Anucleate cells persist for days to weeks.
Dead cells eventually digested by leukocytes.
Liquefactive necrosis
Seen in focal bacterial and fungal infections since they stimulate rapid accumulation of inflammatory cells which digest the tissue.
Hypoxic death of CNS cells results in this.
Gangrenous necrosis
Not a distinctive pattern, usually refers to coagulative necrosis of a limb that has lost its blood supply. If it is liquefactive, it is called Wet Gangrene.
Caseous necrosis
Cheese-like friable yellow-white appearance of necrotic area. Usually seen in TB infection.
Appears on stain as collection of fragmented cells with amorphous appearance. Often surrounded by a collection of macrophages.
Fat necrosis
Focal areas of fat destruction. Lipases leak out of cells and trigger saponification of Ca and fat. Creates visibly chalky deposits.
Fibrinoid Necrosis
Complexes of antigens and antibodies are deposited on the walls of blood vessels.
Mitochondrial Pathway
Intrinsic pathway, triggered by release of cytochrome c into the cytoplasm by the mitochondria. Starts when mitochondrial membrane becomes permeable.
BCL-2
In healthy cells it maintains the integrity of the mitochondrial membrane by keeping Bax and Bak in check.
BH3 proteins
Cna activate Bax and Bak to dimerize and insert into the mitochondrial membrane and form channels.
Cytochrome C
Triggers the caspase cascade leading to apoptosis.
Death receptor Pathway
Surface “death receptors” such as Type 1 TNF receptor and Fas (CD95) receptor.
Fas Ligand (FasL)
Expressed on activated T cells. Trigger these cells to kill their target.
Hypoxia/Ischemia Mechanism of cell death
In cells deprived of oxygen their energy dependent metabolic pathways fail, leading to death by necrosis. Failure of ATP generation, ATP depletion leads to reduced activity of ATP pumps, increase in glycolysis.
Irreversible damage to mitochondrial and lysosomal membranes.
Oxidative stress
Can cause membrane damage, protein misfolding, and mutations.
Endoplasmic Reticulum stress
Caused by misfolded proteins. Adaptive unfolded protein response increases production of chaperones and decreases protein translation to decrease the load.
Terminal unfolded protein response can trigger activation of BH3 family proteins to activate the intrinsic apoptosis pathway.
Hypertrophy
Enlargement of cells, resulting in increase in size of the organ.
Hyperplasia
Increase in the number of cells in an organ. Can take place only if the tissue is capable of replication.
Atrophy
Shrinkage in the size of cells by the loss of cell substance.
Metaplasia
A change in which one adult cell type (epithelial or mesenchymal) is replaced by another adult cell type. Ex. Smoker’s lungs, chronic GERD
Autophagy
Self eating of the cell. Survival mechanism is nutrient deprived. An autophagic vesicle is formed around some cytoplasmic organelles, then it merges with the lysosome and is digested. Can eventually lead to apoptosis.
Intracellular accumulations
Cells may accumulate abnormal amounts of various substances by one of four ways:
Inadequate removal of substance
Accumulation as a result of acquired defects
Failure to degrade a metabolite
Deposition of an abnormal exogenous substance.
Steatosis
Fatty change. Accumulation of triglycerides within parenchymal cells.
Alpha1- antitripsin deficiency.
Mutations in the protein slow folding, resulting in build up of partially folded intermediate, that aggregate in the ER. Resultant deficiency in circulation causes emphysema.
Glycogen storage disease
Enzymatic defects in synthesis and breakdown of glycogen result in massive accumulation in the cell.
Exogenous material ingestion
Carbon a common air pollutant. Aggregates in lymphnodes and pulmonary parenchyma causing anthracosis and blackening.
Pathologic calcification
Abnormal deposition of calcium salts.
Dystrophic calcification
Ca metabolism is normal, but it deposits in injured or dead tissues.
Metastatic calcification
Associated with hypercalcemia, can occur in normal tissues. Can deposit in layers resulting in psammoma bodies.
Major causes of metastatic calcification:
- Increased secretion of parathyroid hormone.
- Destruction of bone due to effects of accelerated turnover.
- Vitamin-D related disorders.
- Renal failure.
