Cell Injury, Adaption & Death Flashcards
(38 cards)
What is cell adaptation?
The structural and functional changes a cell undergoes due to changes in their microenvironment
What are the microenvironmental changes a cell undergoes?
- Physiological (stress, increased demand or hormonal influence)
- Pathological (injurious stimuli)
Why does cell injury occur?
If cells cannot adapt accordingly to changes in their environment, they undergo cell injury.
Cellular Response to Stressors
- Adaptation
- Cell Injury (if cell injury is continuous > cell death
Role of Lysosomal Enzymes in Cell Injury
Lysosomal damage causes leakage of hydrolytic enzymes > break down of cellular components > damage to the surrounding tissue > necrosis
Role of the Sodium-Potassium Pump in Cell Injury
Responsible for movement of K+ into the cell while simultaneously removing Na+ out of the cell.
Failure of the sodium potassium pump can cause the cell to swell + rupture
ATP production in the cell
What is the main cause of cell injury and what is that caused by
Hypoxia: AKA oxygen deficiency
- can be caused by:
- Ischemia (restriction in blood supply to tissues) - most common cause
- Reduction on O2: anemia, CO toxicity
- Decreased tissue perfusion: cardiac failure and shock
- Poor oxygenation of blood: pulmonary diseases
Other causes of cell injury
Physical, chemical and infectious agents
Free radicals
Nutritional deficiencies
Genetic abnormalities
Mechanisms of cellular injury
- Mechanical disruption - trauma / osmotic pressure
- Deficiency of metabolites - glucose, oxygen, hormones
- Failure of membrane functional integrity - damage to ion pumps
- Membrane damage - free radicals can cause damage to DNA
- Blockage of metabolic pathways - interruption of protein synthesis / respiratory poisons e.g. cyanide poisoning inhibits cytochrome oxidase
How does thombus formation lead to ischemic induced cell injury?
Thrombus formation in an artery lead to ischemia of the tissue.
> anaerobic glycolysis > formation of lactic acid and an acidic pH inside the cells.
Cells try to remove H+ which leads to entry of Ca+ inside the cells > activates phospholipases > cell membrane damage
Also anaerobic glycolysis lead to less ATP formation and therefore affecting sodium-potassium pump.
All these lead to cell injury or cell death
Mechanisms of radiation induced cell injury
leads to apoptosis or necrosis
If cells are exposed to a low dose (300-1000 R) - mainly breaks down water which liberates OH- (free radical) which causes damage to the tissue ultimately leads to apoptosis
High doses (<2000 R) - cell and membrane bursts - causes cell death by necrosis
Free radical
An atom/group of atoms containing one or more unpaired electron
Cell injury: mediation by free radicals
interacts w/surrounding tissue, gains an electron - damages the structure of the tissue and impairs function
Mechanism of generation:
Oxygen therapy: > 20% Oxygen therapy
Inflammation
ionizing radiation: radiotherapy
Ultraviolet light
Drugs and chemicals: Barbiturate toxicity (induction of P-450 enzyme in SER)
Consequences of free radicals
Membrane damage
DNA damage
Protein cross-linking
Loss of enzymatic activity
Where are free radicals produced continuously in the body?
Free radicals (superoxide and hydrogen peroxide) are continuously produced in the mitochondria and cytoplasm as a result of metabolic activity
Generation and detoxification of free radicals in a cell
Free radicals are detoxified by:
- superoxide dismutase - an enzyme that facilitates the breakdown of the superoxide into either O2 or H2O2.
Hydrogen peroxide is also damaging, but less so than the superoxide radical - catalase - degrades H2O2 in the body
- Glutathione peroxidase - reduces hydrogen peroxide to water to limit its harmful effects.
What are the cells responses to injury?
- Adaptation - adjusting their structure and functions for various conditions
- Reversible Injury
a) Hydropic degeneration (cloudy swelling) - due to accumulating of water in the cell - commonly caused by Na-K+ pump function failure
b) Fatty change - lipid accumulation die to ribosomal function failure - Irreversible injury = cell death (necrosis/apoptosis)
Cell Injury - Morphological changes
Reversible injury:
Cellular swelling, large vacuoles in the cytoplasm
Swelling of endoplasmic reticulum
Swelling of mitochondria
Disaggregation of ribosomes
Chromatin clumping
Cell blebs
Irreversible cell injury - why & processes?
Severe and prolonged injury leads to the “point of no return”.
Cells cannot recover even if the pathological stimulus is removed.
Either physiological (there is pain AKA necrosis) or pathological (occurring in the body constantly - person is not aware AKA apoptosis)
Necrotic vs Apoptotic cell death
Apoptosis - cell shrinks- fragmentation into membrane-bound apoptotic bodies containing cytoplasmic and nuclear contents - phagocytosed by neighboring cells
Necrosis - cell swells - cell becomes leaky - cellular and nuclear lysis causes inflammation
Necrosis (in detail)
The death of cells in living tissues characterised by the breakdown of cell membranes
Pathological condition
Digestion and denaturation of cellular components by hydrolytic enzymes from damaged lysosomes
Nuclear changes:
- Pkynosis: shrunken, deeply stained
- Karyorrhexis: nucleus fragmentation scattered in cytoplasm
- Karyolysis: nucleus disappears
Associated with inflammatory reaction.
Main types of necrosis
- Coagulative
General architecture well preserved
increased cytoplasmic binding of acidophilic dyes
Nuclear changes
Most often results from interruption of blood supply- Liquifactive
e.g. necrosis in the brain
Enzymatic liquefaction of necrotic tissue
Also occurs in areas of bacterial infected infarction
Abscess formation
- Liquifactive
Caseous
dead cells persist as coarse granular cheese-like debris
shares features of coagulation and liquefaction necrosis
most commonly seen in TB
