May 02, 2023
In reaction to injury, the cell goes through a number of modifications that might or might not result in cell death. The process of cellular adaptation, which cells engage in to endure the adverse changes in their environment, is triggered by harmful stimuli. Cell damage results from overworked adaptive systems. Reversible damage is caused by mild stressors. Injury becomes irreversible if the stimulus is strong or prolonged. The cell membranes, mitochondria, protein synthesis machinery, and DNA are the main targets of cell damage.
DNA-a deoxyribonucleotide polymer that serves as the foundation for all cells' genetic makeup. Although DNA in eukaryotic and prokaryotic organisms is typically double-stranded, several crucial biological processes briefly involve single-stranded regions.
Cell death is a result of numerous cellular abnormalities brought on by the damage. Necrosis and apoptosis are the two primary forms of cell death.
Necrosis is a pathological cell death associated with inflammation whereas apoptosis is a Programmed cell death and it can occur due to both physiological or pathological causes.
Read this blog further to get a quick overview of this important topic for pathology and ace your NEET PG exam preparation.
Cell injury occurs when the maximum adaptive response to physiologic or pathologic stimuli is exceeded or cells are unable to adjust. It occurs in relation to harmful stressors, nutritional loss, or mutations.
There are 2 types of cell injuries
Hypoxia is the most important cause of cell injury whereas the most common cause of hypoxia is ischemia.
Cells which are most resistant to hypoxia are brain cells. Continuous hypoxia of 3-5 minutes leads to death of brain cells.
Cells which are most resistant to hypoxia are fibroblasts.
Reversible cell injury
Irreversible cell injury
Due to hypoxia there is mitochondrial dysfunction as we know that mitochondria is the powerhouse of the cell. This leads to decrease in atp production.
This decrease in atp production leads to:
In a normal cell there is exchange of three sodium to two potassium i.e. 3 na move out of the cell whereas 2 potassium enters inside the cell. This exchange of ions occurs with the help of ATP. In case when there is decrease in ATP synthesis then this pump stops working and now three sodiums will be moving inside the cell whereas two potassium will be going out. As a result there will be more ions inside the cell due to which the water starts moving inside the cell leads to cellular swelling. This is known as hydropic change and also the 1st morphological change which can be seen in cell injury.
Due to this cellular swelling the organelles inside the cell also start to swell and then the endoplasmic reticulum also swells up and the microvilli present on the surface of endoplasmic reticulum flattens this is known as flattening of endoplasmic reticulum.
Cytoplasmic blebs can also be seen due to excessive amount of water inside the cell.
These are derived from membranes of the cell. These are concentric lamellations which are made up of phospholipids and calcium.
Myelin figures are seen in both reversible and irreversible cell injury.
Due to decrease in ATP production there is excessive accumulation of lactic acid which leads to decrease in ph i.e it becomes more acidic and it leads to nuclear chromatin clumping.
Due to decrease in atp the ribosomes which are attached on the surface of endoplasmic reticulum detached which leads to further decrease in protein synthesis and there will be excessive accumulation of fat so this is known as the fatty change.
On microscope the hydropic change in kidney appears as cloudy swelling kidney as due to entry of excessive amount of water the cells of the kidney starts to appear as white.
There are 2 defining moments in irreversible cell injury:
1. Severe membrane damage
2. Severe mitochondrial damage
The membrane is the barrier which prevents certain substances to directly enter inside the cell. When the membrane of the cell is damaged then there is influx of calcium inside the cell and this calcium activates the enzyme as calcium is the cofactor for enzyme activation. It activates phospholipase, nuclease and protease which leads to cell death. Calcium enters inside the cell and attaches to mitochondria, this is known as amorphous flocculent densities.
Nuclear change of the cell in irreversible cell injury:
Pyknosis: shrinkage of chromatin material is known as pyknosis
Karyorrhexis: The irreparably broken down nucleus of a dying cell, with its chromatin dispersed erratically throughout the cytoplasm.
Karyolysis: Complete destruction of chromatin material is known as karyolysis.
Pathological cell death associated with inflammation. It is a passive process i.e. it does not require ATP. Morphological changes in a tissue after cell death occurs
Localized area formed due to ischemia, usually triangular in shape. Apex of infarct points in the direction of site of obstruction.
Hydrolytic enzyme activation causes damage to tissues (liquefied) in this Structural outline not preserved microscopically · Examples
CNS Ischemia → damage to glial cells leading to hydrolytic enzyme activation
Infections → associated with pus formation in Staphylococcus aureus infection
It is Associated with organs with high fats or with high concentration of lipases.
Seen with injury to breast tissue, omentum tissue injury and pancreatitis Acute Pancreatitis
GallStones / Alcohol
Fatty Acids + Ca
Saponification ('Chalk-like' yellow white deposits)
Sr. Ca level (↓↓) is an important prognostic factor to assess the severity of pancreatitis.
Endothelial Cell Injury
Immune Complex formation
Entry or leakage of plasma protein to the vessel wall
Inside the vessel wall (seen as pinkish appearance in the vessel), there is deposition of plasma protein
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Apoptosis is a type of caspase-dependent programmed cell death. · It is controlled by genes, and it affects a single cell or a small group of cells.
Intrinsic / mitochondrial pathway
BCL-2 replaced by BAK / BAX
↑ Cytochrome-C in cytoplasm
Activation of APAF-1 (Apoptosome)
↑ Activation of Caspase 9
Stimulate Caspase 3/ 6/ 7
↑ Activation of Proteases & Endonucleases
FAS –L / TNF α Release (in severe damage)
FAS –L / TNF α + FAS –L / TNF-R
Trimerization ↓ Activation of FADD
Pro CASPASE 8/ 10 → Caspase 8/ 10
↑ Activation of Caspase 3 /6 /7
↑ Activation of Proteases & Endonucleases
Cysteine containing special proteases acting on targets at the aspartic acid residues.
|Caspase Type||Intrinsic pathway||Extrinsic pathway|
|Initiator||Caspase 9||Caspase 8 (Worms), Caspase 10 (Humans)|
|Executioner||Caspase 3/6/7||Caspase 3/6/7|
Cell shrinkage: Cell size decreases due to damage to structural proteins.
No cell membrane damage as there is no activation of phospholipase enzyme.
No Inflammation Tests to Detect Apoptosis.
In gel electrophoresis we can detect the type of cell injury.
It is Done by using ANNEXIN 'V' which attaches to flipped molecules or by using DAPI Stain.
It is a Caspase-Independent programmed cell death.
TNF + TNF-
RIP 1 / 3 [Receptor Interacting Protein Kinase]
Phosphorylation of MLKL Protein
↓PM damage & Inflammation ⊕
o Physiological→ Mammalian Growth Plate
Pathological → Pancreatitis, Reperfusion injury, Parkinsonism, Steatohepatitis
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