Cellular Pathology Flashcards
what is the overall cause of cell injury?
disruption of cellular homeostatic mechanisms
describe cellular injury as a consequence of calcium overload
- first, some agent injures the cell and the result is increased Ca2+ (can come from injurious agent itself, the mitochondria, or the ER)
- increased cytosolic Ca2+ has 4 major effects:
1. affects ATPase: leads to decreased ATP
2. affects phospholipase: decreased phospholipids
3. affects proteases: disruption of membrane and cytoskeletal proteins
4. affects endonuclease: results in nuclear chromatin damage!! probably clumping of chromatin/formation of heterochromatin
describe the cellular Ca2+ gradient
- Ca2+ is way more abundant than extracellular fluid than it is in the cytosol
- this gradient is maintained by 1) the passive impermeability of the plasma membrane to Ca2+ and 2) ATP - dependent extrusion of Ca2+ from the cell
- disruption of these processes = critical event in lethal cell injury (causes dystropic calcification)
dystropic calcification
macroscopic deposition of calcium salts, results from disruption of Ca2+ permeability barrier and consequent increase in intracellular Ca2+
describe calcification as seen in chronic renal failure
- increased intracellular Ca2+
- impaired renal excretion of phosphate
- result is calcium phosphate salts in the eye, heart, blood vessels
describe cellular adaptations
persistent but sub-lethal
describe reversible injury
- mild and short-lived
- will revert back to normalcy
describe irreversible injury
- severe, doesn’t revert to normalcy
- necrosis, apoptosis, pyroptosis
describe the ways that cell injury can be acquired
- stress that results in unsuccessful adaptation (inability to adapt)
- injurious stimulus
describe basic reversible vs. irreversible injury pathways
- reversible: mild, transient, soon return to normal cell (homeostasis)
- irreversible: severe, progressive, results in necrosis or apoptosis
atrophy
decrease in cell size
hypertrophy
increased cell size
hyperplasia
increased cell number
metaplasia
conversion of one cell type to another (remember how this happens in ADPKD!)
dysplasia
disorderly growth (most cancers start from a dysplastic cell!)
characteristics of normal epithelium
- cadherins (cell-cell adhesion)
- intact basement membrane
describe CIS
- stands for carcinoma in situ
- cadherins no longer functioning, cells are disorderly
- still local, has not metastasized because the cells have not invaded the basement membrane, so they are still confined within the epithelial layer
- therefore, this is treatable!!
describe the time scale of the series of biochemical and morphological that occur with cell injury that is severe enough to cause cell death (slide 15)
- start at homeostasis
- cell injury occurs
- reversible changes:
–> ATP depletion
–> biochemical dysfunction
–> early ultrastructural changes - cell death
- irreversible changes:
–> late ultrastructural changes
–> early light microscopic changes
–> late light microscopic changes
time scale of pathologic findings of cellular responses to injury (slide 15)
- start: normal
- seconds: no change
- minutes: no change
- 15-60 minutes:
–> ER swelling and ribosome dissociation
–> membrane rupture, mitochondrial inclusions - 4-8 hours
–> hypereosinophilia of cytoplasm, other features variable depending on the involved tissue
–> karyolysis, coagulative necrosis, influx of neutrophils
do acute injuries always show characteristic pathologic changes?
no, because when an injury is acute enough to cause rapid death of organism, there often isn’t sufficient time for typical cellular responses to develop
cell injury: decreased ATP
leads to multiple downstream effects
cell injury that involves mitochondrial damage
leads to leakage of pro-apoptotic proteins, as well as decreased ATP
cell injury that involves entry of Ca2+
leads to increased mitochondria permeability and activation of multiple cellular enzymes
what are the effects of cell injury that involves increased reactive oxygen species?
damage to lipids, proteins, and DNA
what are the effects of cell injury that involves membrane damage?
plasma membrane damage leads to loss of cellular components, lysosomal membrane damage leads to enzymatic digestion of cellular components
cell injury that involves protein misfolding, DNA damage
leads to activation of pro-apoptotic proteins
what does anoxia (or any other form of energy deprivation) cause?
- reduction in ATP synthesis and malfunction of the ATP-dependent Na+/K+ pump
- this causes Na+ and water to move into the cell, which = cellular swelling
- this is hydropic or vacuolar degeneration!
- organelles swell (including mitochondria), so less energy made
- cell reverts to anaerobic glycolysis, then pH becomes acidic
- organelles break and disentigrate, membranes curl up into concentric bodies
–> myelin figures: rolled up phospholipid bilayers (need electron microscope to see)
–> clumping of nuclear chromatin
what is the first manifestation of almost all forms of injury to cells?
cellular swelling!
how are myelin figures observed?
- first of all, myelin figures are a manifestation of hydropic degeneration in which phospholipid membranes roll up as organelles break and disintegrate
- they are observed with the electron microscope in the cytoplasm or as an inclusion in mitochondria and autophagic vacuoles
define ischemia
decrease in blood supply to a bodily organ, tissue, or part caused by constriction or obstruction of blood vessels
describe the pathway of cell injury caused by ischemia
- MAIN IDEA: causes clumping of nuclear chromatin and lipid deposition!!!
- ischemia (loss of blood supply) results in hypoxia
- this decreases oxidative phosphorylation in the mitochondria, decreasing ATP production, which leads to 3 things:
1. decreased Na+ pump activity, resulting in influx of Ca2+, H2O, and Na+. also increased efflux of K+. this results in ER swelling, cellular swelling, loss of microvilli, and blebs!
2. increased anaerobic glycolysis, leading to decreased glycogen (b/c using it), and increased lactic acid which decreased pH, causing clumping of nuclear chromatin!
3. detachment of ribosomes, causing decreased protein synthesis and lipid deposition!