Cell Death Flashcards
What is necrosis?
Cell death resulting from either exogenous or endogenous damage. Eventual damage to membrane results in leaking cellular contents
Inner contents of cell come out and spill into extracellular space
What is apoptosis?
Programmed cell death can be result of external or internal cell damage, physiologic, or developmental
Characterized by enzymatic degradation of proteins and DNA (initiated by caspases) and removal of dead cells by phagocytes - Results in cell fragmentation and phagocytosis
Serves to eliminate unwanted and irreparably damaged cells, with the least possible host reaction
What are characteristics of necrosis?
Cell death that is not controlled by the cell and does not require the signal or activation of genes
Changes seen vary with tissue and mechanism of death
Cytoplasmic changes - eosinophilia, glassy appearance, vacuolation
Nuclear changes - pyknosis, karyorrhexis, karyolysis
Characterized by cell and organelle swelling, ATP depletion, increased plasma membrane permeability, release of macromolecules, and inflammatation
What are the types of necrosis?
- Coagulative
- Liquefactive
- Caseous
- Enzymatic Fat
- Fibrinoid
- Gangrenous
What is coagulative necrosis?
Happens in tissue with CT framework
Seen in death due to ischemia, hypoxia, reperfusion injury in most organs except brain
Basic outline of cell preserved but with no nuclei
What is an example where coagulative necrosis will occur?
Myocardial infarction
What is liquefactive necrosis?
Dead cells undergo disintegration and affected tissue is liquefied
Death of brain tissue usually leads to liquefactive necrosis because of lack of supporting CT
Seen in abscess where the center is made up of enzymatic digested neutrophils (pus)
Amorphous, granular under microscope Loss of cells and tissue structure
What are examples of liquefactive necrosis?
Cerebral infarction
Abscess - Acute Appendicitis
What is Caseous Necrosis?
Form of coagulative necrosis (cheese-like)
Accumulation of mononuclear cells that mediate the chronic inflammatory reaction and granuloma formation to the offending organism
Lipid in wall of organism can’t be fully broken down, the dead cell persist indefinitely as amorphous, coarsely granular, eosinophilic debris
Grayish, whitish, or yellowish, soft, friable and cheesy in appearance
What is an example of caseous necrosis?
Tuberculosis lesions
Certain fungi
What is enzymatic fat necrosis?
Enzymatic fat digestion of fat
Fat changed due to action of lipases
Fatty acids that are released react with calcium to form soap-like substance
Looks white, chalky
Microscope shows material in fat cells rather than normal clear appearance
Enough calcium will cause deposits to be basophilic
What is an example of enzymatic fat necrosis?
Pancreatitis - necrosis of fat
Inflammation in fat
What is fibrinoid necrosis?
Always occurs in vessels
Injury in blood vessels with accumulation of plasma proteins causing the wall to stain intensely eosinophilic
Fibrin + Necrotic material
What is gangrenous necrosis?
Usually secondary to ischemia like a limb or bowel
Necrosis affecting multiple tissue types (skin, nerve, muscle, etc)
Can be dry where tissue is mummified
Wet gangrene - combo of gangrene with superimposed bacterial infection
What are examples of dry gangrene?
Diabetes - most common
Snake bite
Cold agglutination
What is ischemia?
Caused by reduction of available oxygen
When it leads to tissue death, you end up with heart attack, stroke, etc
What is reperfusion injury?
When blood flow/oxygenation of the tissue is restored
Ex. Giving clot breaking therapy (TPA) during heart attack and stroke or in transplantation
What does ischemia lead to?
Leads to large amount of ROS damage: O2-, OH. and ONNO.
and lipid peroxide radicals
What are serum blood tests are used to detect a MI?
Tests to detect elevations in creatine kinase - MB (CK-MB) fraction
Troponin I (TnI) or Troponin T (TnT) levels
What do ROS react with?
Lipid peroxide radicals - disrupt plasma membrane and organelles
Oxidation of proteins - abnormal folding of proteins and affects enzyme activity
Oxidation of DNA - mutations, breaks
What are the physiological roles of apoptosis?
Embryogenesis
Hormone dependent involution
Cell deletion in proliferating cell population
Normal immune defense against viral infected or neoplastic transformed cells as cytotoxic T cells clearance
Removal of self-reactive lymphocyte clones
Removal of cells that have served their purpose (inflammatory cells)
What is apoptosis in pathologic conditions?
Cell death in tumors - cytotoxic anticancer drugs
DNA damage from low doses of some agents - radiation, extreme temp, drugs, that would cause necrosis in larger doses
Transplant rejection
Atrophy after duct obstruction
Some viral diseases
What are the stages of apoptosis?
Pathways start apoptosis through release of cytochrome C (intrinsic pathway) or activation of receptor (extrinsic pathway)
- Initiation phase - intracellular signals further commit the cell to apoptotic pathway by production and activation of first wave of initiator caspases
- Execution phase - execution caspases catabolize the cytoskeleton and active endonucleases which cause DNA breakdown
- Removal phase - removal of round dead fragments of cells by macrophages
What is the extrinsic pathway of apoptosis?
Death receptor initiated: Fas (CD95), TNF (tumor necrosis factor) activate adaptor proteins which bind caspases
