Explain the role of ROS in cell injury, including reperfusion injury.
- PROLIFERATING CELLS: DNA damage; Inability to replicate
- NONPROLIFERATING CELLS: Lipid peroxidation of membrane phospholipids; Loss of membrane integrity
- damages to lipids (by peroxidation), proteins, and deoxyribonucleic acid (DNA) result in cell injury, and lead to CELL DEATH
List agents and conditions which protect the cells from Free Radicals, ROS and RNOS imbalance.
- Cellular defenses against free radicals - vit A, C, E
- SOD converts superoxide to hydrogen peroxide and O2
- Catalase converts H2O2 to H2O and O2
Describe how an interruption of oxygen supply leads to cell swelling.
- Decreased ATP from mito
- Decreased ATPase work
- Less Na+ pumped out
- Water comes in
Describe the process of formation of lipid (steatosis) or protein globules within parenchymal cells.
- In healthy liver cells, fatty acid is oxidized or converted to triglycerides, which is then transferred via lipid acceptor proteins. When not healthy, triglycerides accumulate in cells.
- Protein gets to tubule via glomerulus leakage, and is reabsorbed by tubule, forming droplets.
List causes of cell injury.
- Altered stimuli
- Increased demand
- Decreased supply
- Chronic irritation
- Deprivation of nutrient
- Cumulative sublethal injury
Summarize changes in cell morphology following injury.
- Swollen ER, mitochondria, cell
- Clumped chromatin
- damaged membrane with leakage of cellular contents
Healthy cell + stress ->
Healthy cell + injurous stim ->
Adaptation + inability to adapt ->
cell injury + mild, transient -> ____ -> ____
cell injury + severe, progressive -> ____ -> ____
- cell death: necrosis/apoptosis
Adaptation in the form of ____________ or ___________ leads to __________.
- relief of stress and return to normal
High blood pressure results in _____ of myocardium, not _________
- Increased cell numbers
- CDKIncreased cell size and nuclear size
- reversible gingival hypertrophy in response to anti-convulsive medication
- Physiological hypertrophy of uterus during pregnancy
- Myocardial hypertrophy due to high blood pressure
- Normal tissue changes into abnormal one
- Metaplasia of columnar epithelium to squamous epithelium in a bronchus.
- dentin replaced by cementum or bone
- Cells decrease in size, not number
- mRNA of digestive enzyme is sent out, and enzyme is produced and included in or lysosome is fused with the autophagosome formed by SER encircling cellular organelles such as mito when downsizing of the cell is required. mito is digested and the pigmented residual body is transferred out of the cell via exocytosis
- Involved in autotrophy to downsize the cell
- Adaptive response during nutrient deprivation
- Also plays a role in host defense against certain microbes
Autophagy pathway proceeds through several phases: and eventually creates double-membrane-bound vacuoles (autophagosome) in which cytoplasmic materials including organelles are sequestered and then degraded following fusion of the vesicles with lysosomes.
initiation, nucleation, and elongation of isolation membrane
Various external stresses or mutations induce a state called ______, in which the cell is unable to cope with the load of _______. Accumulation in the ER triggers the _________, which tries to restore protein homeostasis; if this response is inadequate, the cell ______.
- ER stress
- misfolded proteins
- unfolded protein response
- dies by apoptosis
Lipofuscin (Lf) pigment in
- a residual body, found in cardiac myocyte w/ atrophy
- fuscin: brown
- aka lipochrome
Replicative senescence - reduced capability of cell to divide secondary to progressive shortening of telomeres.
Cellular aging results from a combination of
- Accumulating cellular damage (e.g., by free radicals) and Reduced ability to repair damaged DNA
- : Defective DNA repair mechanisms; caloric restriction activates DNA repair and prolong aging in model organisms
- Reduced capacity to divide - replicative senescence
- Defective protein homeostasis - impaired chaperone and proteasome functions.
Nutrient sensing system: Caloric restriction increases longevity via Mediators such as reduced ____ signaling and increases in ____.
When telomeres become so short, cell _______; ___ cells and ____ cells can grow indefinitely.
- dies or becomes cancerous
- Germ cells and stem cells both contain telomerase, but only germ cells have sufficient levels of the enzyme to stabilize telomere length completely. In cancer cells, telomerase is often reactivated.
Explain the role of adaptations in cell survival and function.
Summarize changes in cell morphology following injury and adaptation to injury.