7. Apoptosis morphology, pathomechanism

In contrast to necrosis, apoptosis can be physiological. When cells are no longer needed, they are instructed to die by apoptosis, which doesn’t cause inflammation. The cell contents don’t burst into the surroundings but are instead packed into apoptotic bodies that are later removed by macrophages.

Apoptosis is seen in many physiological situations. Some examples:

• During development of your fingers and toes during embryogenesis, the cells between the fingers and toes die by apoptosis
• After weaning, the breast tissue regresses by apoptosis
• The endometrium regularly undergoes apoptosis during the menstrual cycle
• During both T-cell selection in the thymus and B-cell selection in the germinal centre, cells that are not needed die by apoptosis

However, apoptosis can also be found in certain pathological situations. Some examples:

• Cells may die due to DNA damage due to radiation from the sun, or from cytotoxic anticancer drugs
• Accumulation of misfolded proteins leads to the cell dying by apoptosis
• Certain infections can cause cells to undergo apoptosis, like HIV, adenovirus or hepatitis.
• Certain organs undergo atrophy by apoptosis when their ducts are obstructed, like the pancreas, parotid gland or the kidney

Morphology

The morphology of apoptosis is best seen in electron microscopy. The cell shrinks, the cytoplasm becomes denser, and the organelles are more tightly packed. The chromatin in the nucleus condenses and the nucleus itself may break up to fragments. The formation of cytoplasmic blebs (google it) and apoptotic bodies may also be seen with electron microscopy.

You can read more about the mechanism and pathways of apoptosis here.

Pathological correlations

When cells that are dependent on a certain growth factor are deprived of the growth factor, they will undergo apoptosis. This can happen in the cause of endocrinological problems, where certain hormone levels are so low that tissues that are sensitive to this hormone die because of lack of stimulation. Neurons that are deprived of nerve growth factor also die this way.

When there is DNA damage to a cell for any reason (radiation, drugs), a tumor suppressor protein called p53 will stop the cell cycle to allow the cell to repair the damage before duplicating. If the damage cannot be repaired the cell will undergo apoptosis.

Many factors can cause proteins to misfold inside the cell. It happens in genetic mutations, during aging and in neurodegenerative diseases like Alzheimer’s, Huntington’s and Parkinson’s diseases. This triggers the unfolded protein response, that ends with apoptosis.