Cell injury 1 (apoptosis and necrosis) l General pathology MCQs for dental student

Cell injury 1 (apoptosis and necrosis) l General pathology MCQs (multiple choice question)  for dental student

 

Cell injury and cell death

• Cell injury: It occurs when cells exposed to sever stress or damaging agents .It is in 2 types:

• Reversible injury: occurs when the injurious cellular derangements can be corrected, the cell can return to normal function and activity after the stimulus is removed.

• Irreversible injury: occurs when cell exposed to persistent or excessive injury that subjected cells pass the point of no return leading to cell death.

 

Types of cell death:

• Necrosis: is the type of cell death that result from harmful conditions associated with loss of membrane integrity and leakage of cellular contents (lysosomes) and digest the cell.

• Apoptosis: regulated mechanism of cell death that serves to eliminate

• Unwanted and irreparably damaged cells, with the least possible host reaction by activation degradation enzymes.

 

 Causes of cell injury:

• Oxygen Deprivation: Hypoxia is oxygen deficiency while ischemia is loss of blood supply in a tissue leading to hypoxia (pneumonia, anemia or carbon monoxide (CO) poisoning).

• Chemical Agents: poisons, air pollutants, insecticides, CO, asbestos and therapeutic drugs if used excessively or inappropriately.

• Infectious Agents: viruses, tapeworms, rickettsiae, bacteria, fungi, and protozoans.

• Immunologic Reactions: autoimmune reactions against one’s own tissues and allergic reactions against environmental substances in genetically susceptible individuals.

• Genetic Factors: congenital malformations, Down syndrome, subtle as the single amino acid (sickle cell anemia).

• Nutritional Imbalances: iron and vitamin deficiencies, obesity resulting in type 2 diabetes mellitus, diets rich in animal fat are strongly associated with atherosclerosis.

• Physical Agents: Trauma, extremes of temperature, radiation, electric shock and sudden changes in atmospheric pressure.

• Aging: Cellular senescence leads to alterations in replicative and repair abilities of individual cells and tissues.

 

The morphology of reversible cell injury:

• Alterations in Injured Cells and Tissues

Cellular swelling:

• Occur due to failure of energy-dependent ion pumps in the plasma membrane leading to an inability to maintain ionic and fluid homeostasis.

• Microscopic examination may reveal small, clear vacuoles within the cytoplasm (segments of the ER). This pattern of nonlethal injury is sometimes called hydropic change or vacuolar degeneration.

Fatty change:

• Occurs in hypoxic injury and toxic or metabolic injury and is manifested by the appearance of small or large lipid vacuoles in the cytoplasm. It occurs in cells involved fat metabolism (ex. Hepatocytes, myocardial cells).

 

The morphology of irreversible cell injury (necrosis):

• Damage of injured cells

Increased eosinophilia:

• It is pink stain from the eosin dye [H&E] due to increased binding of eosin to denatured cytoplasmic proteins and loss of the basophilia that is normally imparted by the ribonucleic acid (RNA) in the cytoplasm.

Vacuolated cytoplasm and moth eaten :

• Because enzymes that digest the organelles and a more glassy homogenous appearance because of loss glycogen particles.

Nuclear changes:

1. Nuclear changes due to breakdown of DNA and chromatin.
2. The basophilia of the chromatin may fade (karyolysis) because to deoxyribonuclease (dnase) activity.
3. A second pattern is pyknosis characterized by nuclear shrinkage and increased basophilia and DNA condenses into a solid shrunken mass.
4. In the third pattern, karyorrhexis, the pyknotic nucleus undergoes fragmentation.
5. Within 1 to 2 days, the nucleus in a dead cell may completely disappear.

Fates of necrotic cells:

• Necrotic cells may persist for some time or may be digested by enzymes and disappear or may either phagocytosed by other cells or further degraded into fatty acids bind calcium salts resulting in the dead cells ultimately becoming calcified.

 

Patterns of tissue necrosis:

Coagulative necrosis:

• Is a form of necrosis in which the tissue architecture is preserved for at least several days because the injury denatures not only structural proteins but also enzymes blocking the proteolysis of the dead cells, it occurs in all solid organs except the brain.

Liquefactive necrosis:

• Is seen in bacterial, fungal infections because microbes stimulate the accumulation of inflammatory cells and the enzymes of leukocytes digest the tissue and transforming into a liquid viscous mass (creamy yellow and is called pus).

• It occurs also in hypoxic death of cells within the central nervous system.

Gangrenous necrosis:

• It isn’t a pattern of cell death but it is used in clinical practice. It occurs in limb mostly the lower leg that has lost its blood supply and has undergone coagulative necrosis involving multiple tissue layers.

• When bacterial infection is superimposed, coagulative necrosis is modified by the liquefactive action of the bacteria and the attracted leukocytes (resulting in so-called wet gangrene).

Caseous necrosis:

• It is a collection of fragmented or lysed cells, unlike coagulative necrosis the tissue architecture is completely distorted and it enclosed within an inflammatory border (Caseous means cheese-like); this appearance is characteristic of a focus of inflammation known as a granuloma.

Fat necrosis:

• It is a focal area of fat destruction resulting from release of activated pancreatic lipases into the substance of the pancreas and the peritoneal cavity.

Fibrinoid necrosis:

• It occurs when reactive immune antigens and antibodies complexes are deposited in the walls of arteries with fibrin that has leaked out of vessels forming fibrinoid.

Mechanism of cell injury:

1. ATP depletion: failure of energy-dependent functions → reversible injury → necrosis
2. Mitochondrial damage: ATP depletion → failure of energydependent cellular functions → ultimately, necrosis; under some conditions, leakage of mitochondrial proteins that cause apoptosis
3. Influx of calcium: activation of enzymes that damage cellular components and may also trigger apoptosis
4. Accumulation of reactive oxygen species: covalent modification of cellular proteins, lipids, nucleic acids
5. Increased permeability of cellular membranes: may affect plasma membrane, lysosomal membranes, mitochondrial membranes; typically culminates in necrosis
6. Accumulation of damaged DNA and misfolded proteins: triggers Apoptosis.

Apoptosis

• Regulated mechanism of cell death that serves to eliminate unwanted and damaged cells, with the least possible host reaction.

• Characterized by enzymatic degradation of proteins and DNA, initiated by caspases; and by recognition and removal of dead cells by phagocytes. It is initiated by two major pathways:

Mitochondrial (intrinsic) pathway :

• Is triggered by loss of survival signals, DNA damage and accumulation of misfolded proteins (ER stress); associated with leakage of pro-apoptotic proteins from mitochondrial membrane into the cytoplasm, where they trigger caspase activation; inhibited by anti-apoptotic members of the Bcl family, which are induced by survival signals including growth factors.

Death receptor (extrinsic) pathway :

• Is responsible for elimination of self-reactive lymphocytes and damage by cytotoxic T lymphocytes; is initiated by engagement of death receptors (members of the TNF receptor family) by ligands on adjacent cells.