Irreversible cell injury - cell death. Types of necrosis; microscopic & gross pathomorphology. Apoptosis.
As cells undergo extensive stress they will try to adapt, where that adaptation becomes irreversible adaptation the cell is forced down the path of cell death. As we know, cell death can be Necrosis (unplanned) or Apoptosis (planned). Some causes of cell injury include:
- Hypoxia and Ischaemia
- Physical agents
- Chemical agents
- Microbiology
- Immunological agents
- Nutritional factors
- Aging
- And others
These factors result in some common pathogenetic pathways that damage the cell:
- Many of these etiological factors ultimately lead to failure of ATP generation and ATP depletion
- This reduces activity of ATP dependent Na⁺/K⁺ pumps
- Results in sodium (and therefore water) accumulation in cell
- Therefore causes cellular swelling
- Failure of calcium pump leading to membrane damage
- Compensatory increase in anaerobic glycolysis leads to build up of lactic acid
- decreased intracellular pH as a result
- Decreased enzyme activity
- Prolonged ATP depletion results in detachment of ribosomes from rER
- Hypoxia also seems to increased ROS concentration, causing lipid peroxidation on cell membrane, cross linking of proteins and DNA damage
Where the damage to the cell is persistent or excessive, injured cells pass the point of no return and their damage becomes irreversible, there are three key indicators for this point:
- Inability to restore mitochondrial function
- Structure and function of plasma membranes and intracellular membranes
- The loss of DNA and chromatin structural integrity
Necrosis - Types of Necrosis
Necrosis is the local death of cells, tissues, part or sometimes an entire organ, there are two essential changes that characterise all types of necrosis:
- Cell digestion by lytic enzymes
- Denaturation of proteins
The key cytoplasmic changes are:
- A homogeneous cytoplasm
- Which appears highly eosinophilic due to increased binding of eosin to denatured proteins
Nuclear changes to the cell can be seen as:
- Karyopyknosis (Nuclear shrinking)
- Karyorrhexis (Nuclear fragmentation)
- Karyolysis (Nuclear fading)
There are five types of Necrosis, these are:
- Coagulative necrosis (e.g. Necrosis Renis and Necrosis Myocardium) (NOTE SLIDES FOR BOTH)
- Liquefactive necrosis (e.g. Necrosis cerebri) (NOTE SLIDE)
- Caseous necrosis (e.g.. Necrosis Lymphonodi) (NOTE SLIDE)
- Fat necrosis
- Fibrinoid necrosis
Coagulative necrosis
This is the most common form of necrosis and is the result of hypoxic death of cells in all tissues except for the brain. It is the result of denaturation of proteins and blocked proteolysis.
The gross morphology shows a sharply demarcated line, with a grayish-white zone surrounded by a hemorrhagic zone.