Causes of Apoptosis:

It is divided into two groups;

1. Apoptosis in physiological situation
2. Apoptosis in pathologic condition

a. Apoptosis in physiological situation:

• Programmed destruction of cells during embryogenesis/organogenesis. Normal development is associated with death of some cells and appearance of new cells and tissues.
• Involution of hormone-dependent tissues upon hormone deprivation. Ex: lactating animals during lactation have developed mammary gland due to action of prolactin, but after weaning, these cells undergo apoptosis and lactating mammary gland regresses. Also, prostatic atrophy of testicle after castration.
• Cell loss in proliferating cell population such as in crypts of GIT, in order to maintain constant number.
• Elimination of cell that served their useful purpose such as neutrophils in acute inflammatory response and lymphocytes at end of immune response. They undergo apoptosis because of deprivation of necessary survival signals, such as growth factor.
• During hematopoiesis, many blood cells undergoes apoptosis to maintain normal circulation.
• Elimination of potentially harmful self-reactive lymphocytes: During development of immune system many lymphocytes goes to thymus and develop into T-cell and develops TCR. During process, some T-cell develops TCR which react with own antigen. These T-cells are called autoreactive T-cell. They undergo apoptotic process and reduces chances of autoimmune disease.

b. Apoptosis in pathologic condition:

• This eliminates the cell that are genetically altered or injured beyond repair. It occurs without eliciting severe host reaction. So, tissue damage will be minimum.
• DNA damage: When DNA is damaged by radiation, cytotoxic anticancer drugs, extreme temperature, hypoxia. If repair mechanism cannot cope with injury, cell triggers intrinsic mechanism that induce apoptosis. This elimination of cell reduced the risk of mutation which may progress to malignant transformation.
• Cell injury in certain infection like viral infection, injured cell undergoes apoptosis that may be induced by virus or by host immune response (cytotoxic T-cell).
• Pathologic atrophy in parenchymal organs after duct obstruction such as pancreas, parotid gland and kidney.
• Accumulation of misfolded protein: Improperly folded protein may arise due to mutation in genes or extrinsic factors. Excessive accumulation of these proteins in ER leads to condition called endoplasmic reticulum stress, which results in apoptosis.