CELL INJURY, ADAPTATION & DEATH Flashcards
Etiology
origin of a disease, including underlying causes and modifying factors
- why a disease arises
Pathogenesis
the development of a disease from the initial etiologic trigger to the cellular and molecular changes that give rise to specific functional and structural abnormalities that characterize a specific disease
- how/mechanisms of a disease develops
Morphology/Morphologic abnormalities
changes in the macroscopic or microscopic appearance of cells and tissues and their constituents, as well as biochemical alterations in body fluids
- how pathogenic mechanisms manifest at the cellular/organelle level
Hypertrophy
a regulated process in which there is an increase in cell/tissue size as an adaptive mechanism to stress
- involves signaling mechanisms and mediated changes with feedback loops for added regulation
Atrophy
another highly regulated process involving the regression/lack of function of a cell/tissue
- mediated by mechanisms like lysosomal activity and ubiquitin-proteosome pathway of protein degradation
Physiological atrophy
physiological structures may naturally undergo atrophy and have to clinically be tested to see if an abnormal growth
Pathological atrophy
disuse, denervation, ischemia
Metaplasia
change of one epithelial type to another
- often a protective measure to adapt to stressor
Necrosis
“accidental” and unplanned cell death in response to harmful trigger
- in this event, there is evidence of cell injury: cellular membranes fall apart, cellular enzymes leak out and ultimately digest the cell, followed by an accompanying inflammatory reaction
- characterized by cytoplasmic changes showing increased eosinophilia and pyknotic (shrunken) nuclei with increased basophilia
- is ALWAYS pathologic
Apoptosis
programmed cell death that does not elicit host inflammatory response
- not always pathologic
Necroptosis
a form of cell death that shows features of both necrosis and apoptosis
- triggered by RIPK1 and RIPK3 signaling that leads to phosphorylation of MLKL which then forms pores in the plasma membrane
Pyroptosis
cell death induced by inflammasomes that release cytokine IL-1 which cause inflammation and fever
Ferroptosis
cell death dependent of the level of iron induced by lipid peroxidation
- not very well understood mechanism of cell death
Common sites of cell injury
mitochondria, intact cellular membranes and the nucleus
- these are critical sites for many cellular processes making them vulnerable
Mitochondrial injury
triggered by hypoxia/ischemia, radiation, other injurious agents with consequences of failed oxidative phosphorylation yielding less ATP generation 2. abnormal oxidative phosphorylation resulting in the production of reactive oxygen species
- affects mitochondrial proteins as well
- necrosis OR apoptosis
Cellular membrane injury
triggered by reactive oxygen species and other injurious agents resulting in leakage of enzymes/cellular contents and impaired transport functions
- often results in necrosis
Nuclear injury
triggered by radiation and mutations resulting in impaired cell signaling, DNA damage, etc
- typically leads to apoptosis
Consequences of calcium influx
activation of cellular enzymes that result in membrane damage, nuclear damage and decreased ATP production
Anoikis
apoptotic death due to loss of cell matrix interaction
- cell is in the wrong environment, it won’t “interact” with cell matrix because not suitable for it
coagulative necrosis
cells/tissue takes on a firm texture due to denaturation of structural proteins and enzymes, limiting the amount of proteolysis of the dead cells which results in the persistence of eosinophilic, anucleate cells
- characteristic of infarcts of tissue due to ischemia (i.e an MI)
liquefactive necrosis
microbes stimulate the accumulation of inflammatory cells and the enzymes of leukocytes digest (“liquefy”) the tissue
- the dead cells are competely digested, turning the tissue into a viscous liquid that is later removed by phagocytes
- fluid= pus; localized pus= abscess
- i.e hypoxia in the brain/CNS often results in liquefactive necrosis
Gangrenous necrosis
usually refers to the condition of a limb (generally the lower leg) that has lost its blood supply and has undergone coagulative necrosis involving multiple tissue layers
- not a distinctive pattern of cell death
caseous necrosis
often surrounded by a collection of macrophages and other inflammatory cells, giving a holey “cheese-like” appearance
- i.e a granuloma
Characteristics of apoptosis
appear as single cells, nuclear fragmentation, lack of inflammation, cell shrinkage, intact cell membrane and is often physiologic
