Chapter 2 Cell injury, cell death and apoptosis Flashcards
Etiology
the underlying causes and modifying factors that are responsible for the initiation and progression of disease.
(why a disease arises)
pathogenesis
the mechanisms of development and progression of disease.
how the disease develops
how does cell injury occur?
when the external stress on a cell exceeds the cells ability to adapt to that stress.
to some degree the cell can recover from the injury.
(lack of blood flow, infection, toxins, immune reaction)
hypoxia and ischemia cell damage caused by?
arterial obstruction
inadequate oxygenation of the blood
reduced oxygen-carrying capacity of the blood (anemia)
CO poisoning.
general examples toxins that affect cells?
air pollutants insecticides CO asbestos cigarette smoke ethanol drugs.
categories of injurious stimuli to cell?
Toxins infectious agents immunologic reactions genetic abnormalities nutritional imbalances physical agents aging
Reversible cell injury morphology?
organelles become swollen as they take in water due to the failure of pumps. Increased permeability of cell membranes. this causes pallor (due to vessel compression) and increased turgor and increase in organ weight.
loss of microvilli, mitochondrial swelling.
signs of reversible cell injury? 4 of them
1 plasma membrane alterations such as blebbing, blunting, or distortion of microvilli, and lossening of intercellular attachement
2 mitochondria changes such as swelling and the appearance of phospholipid-rich amorphous densities.
3 dialtion of the ER with detachment of ribosomes and dissociation of polysomes
4 nuclear alterations such as clumping of chromatin
what causes the smooth endoplasmic reticulum to swell?
the smooth ER swells as a response to various chemicals that are processed by the p450 enzymes in the smooth ER.
this adaptation results in the need to increase the dose of the drug as treatment proceeds. the p450 can also make harmless drugs into toxic ones such as CCl4.
Necrosis vs apoptosis?
Necrosis is the “accidental cell death” due to lack to nutrients or oxygen, toxins, trauma causing the cell to fall apart. cell contents are released during cell death.
Apoptosis: programmed cell death of healthy cells.
NECROSIS: pathological APOPTOSIS: healthy cell death.
morphology of necrosis, cytoplasmic changes
the cell becomes more eosinophilic due to the accumulation of denatured proteins. and becomes less basophilic (blue) due to the less glycogen particles. The cytoplasm becomes vaculated.
name the 3 potential changes to the nucleus due to necrosis?
- Pyknosis: nuclear shrinkage and increase basophilia. DNA condenses.
- Karyorrhexis: the pyknotic nucleus undergo fragmentation.
- Karyolysis: the basophilia fades due to digestion of DNA by DNase.
Fates of necrotic cells?
digested by enzymes and replaced by myelin figures which can be phagocytosed by other cells or further degraded into fatty acids. the Fatty acids bind Ca2+ slats which may result in the dead cells ultimately becoming calcified.
Coagulation necrosis?
a types of necrosis in which the underlying tissue architecture is preserved for at least several days after death of cells in the tissue, later removed by leukocytes and phagocytosed by neutrophils and macrophages.
Example: infraction.
Liquefactive necrosis?
seen in focal bacterial and occasionally fungal infections, due to microbes stimulate rapid accumulation of inflammatory cells and the enzymes of leukocytes digest (liquefy) the tissue.
the acute inflammation results in the creamy-white material (PUS).
Gangrenous necrosis?
when an entire limb looses its blood supply and undergo coagulative necrosis and superimposes with bacterial infection. resulting in “wet gangrene”.
Caseous necrosis?
“cheese like” appearance as the cells are completely obliterated and cellular outlines cannot be discerned. surrounded by macrophages.
Fat necrosis?
areas of fat destruction due to activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity. The leaking pancreatic enzymes liquefy the membranes of fat cells in the peritoneum and lipases release fatty acids that combine with Ca2+ to form a glossly visible chalky white areas.
fibrinoid necrosis?
occurs in immune reactions in which complexes of antigens and antibodies are deposited in the walls of blood vessels, but it also may occur in severe hypertension. the leak of plasma proteins into the wall of damaged vessel produce a bright pink amorphous appearance.
why does necrosis cause inflammatory response while apoptosis does not?
necrosis results in the release of cellular contents resulting in an inflammation response while apoptosis does not.
physiological apoptosis?
in normal organs old cells undergo apoptosis to be replaced by new ones to regulate their growth.
In the immune system the apoptosis eliminates excess leukocytes left over from an immune response. Lymphocytes that recognize self-antigens that could cause autoimmune diseases if they were not phagocytosed.
what causes apoptosis in pathologic conditions?
- severe DNA damage (radiation and cytotoxic drugs exposure.)
- accumulation of misfolded proteins.
Apoptosis is regulate by?
a balance of death and survival inducing signals and activation of enzymes called CASPASES.
what are the 2 pathways for apoptosis?
- death receptor pathway
- mitochondrial (intrinsic) pathway.
