Types and causes of cell death

There are two types of cell death:

A) Necrosis:

The uncontrolled cell death that occurs as a response to lethal injury leading to a severe physical damage in the cell as well as the tissue containing it. This is usually not an energy-dependent active process but a result of a sudden abnormal change in the microenvironment that destroys the function of the cell.

There are three principal forms of necrosis:

1) Coagulative necrosis which results in the loss of nuclei from the dying cells. This injury not only cause the denaturation of the vital proteins for cellular structure, cytoplasm and nucleus but also abolish the enzymes within the lysosomes that would otherwise damage the intracellular and extracellular components. In fact, this is the most common type of necrosis that occurs in solid organs , such as heart and kidney. This usually happens as a result of severe ischamia which results in the destruction of proteolytic enzymes.


This histological image shows coagulative necrosis in uterine corpus leiomyoma. Image in courtesy of https://commons.wikimedia.org/wiki/File:Uterine_leiomyoma_%283%29_with_ischemic_necrosis.jpg

     Coagulative necrotic cells appearance usually show initial preservation of cellular outline and architecture of the tissue. However, tissue apperance does not remain in a necrotic state forever. This is because these cells release digestive enzymes that degrade the cellular components and the resulting debris is then cleared by phagocytes.

2) Colliquative or liqueative necrosis whose main feature is the release of strong hydrolytic enzymes that result in the destruction of both cellular components and extracellular materials and formation of a proteinacceous soap. This type commonly occurs in the brain (cerebral infarction) where it generates a cystic cavity consisting of necrotic debris and fluid.

    Liquefaction might also take place in tissues that has been exposed to a bacterial infection. In this case, the enzymes will be released by both the invading bacteria as well as the inflammatory cells recruited to fight them.

An illustration of liqueative necrosis due to a chronic bacterial infection in a bovine respiratory tract

 3) Caseous necrosis is the type of necrosis where the tissue loses its outline and is converted into a dry mass resembling soft cumbly cheese. Under microscope, the necrotic area appears homogeneously pink and surrounded by inflammatory response including macrophages, multinucleate giant cells and lymphocytes. This type of necrosis typically appears in tuberculosis.

This histological image is showing caseous necrosis in a tissue suffering from pulmonary tuberculosis. Image in courtesy of usmlewiki.org/index.php?title=Image:Caseous_necrosis.png  

 Main Causes of Necrosis:

1) Any physical damage that overwhelm cell programmed death, such as drying, trauma and excessive DNA damage. 

2) Infections, such as dengue.

3) Acute (or chronic) toxicity, Mercury poisoning is an example.

4) Rapid loss of energy, such as the loss of energy caused by the electron chain in mitochondria.


B) Apoptosis (main type of programmed cell death).


This is the type of cell death that occurs deliberately under physiological and genetic control, which involves a single cell or a small group of cells in a tissue. Unlike necrosis, in apoptosis, other cells in the tissue are not affected and functioning normally.  In fact, the word apoptosis is a Greek derivative which was originally used to describe the falling of individual leaves from a tree.


Main features of apoptosis:

1) Cell Shrinkage and condensation.

2) Cytoskeletal collapse.

3) Nuclear disassembly, and condensation and fragmentation of its chromatin.

4) Formation of apoptotic bodies following the disintegration of the cellular surface.

4) Phagocytosis of the apoptotic bodies by immune cells, such as macrophages, and epithelia adjacent to the cell.   


Apoptosis often is associated with:

A) Developmental cell loss.

An example of this is the development of mammalian limb with the five fingers. In fact, this process involves two steps. Firstly, the growth of the tissue occurs by cellular division. Secondly, it is important that interdigital cell death happens as well otherwise a webbed limb will develop rather than a five digit limb.


This histological image shows webbed hand due to apoptosis abnormalities.Image in courtesy of https://commons.wikimedia.org/wiki/File:New_born_boy_showing_complete_complex_syndactyly_with_two_fingers_right_hand.JPG

Another example is the death of tail cells at metamorphosis as tadpoles develop into adult frogs. This results in the disappearance of the tail as it is not required in the frog. In other cases, apoptosis occurs for the regulation of cell numbers. For instance, in the developing nervous system, it occurs to match the number of neurons to the number of target cells they innervate.  

B) Cell Senescence (cell replicative senescence), where cells slow proliferation and eventually ceases irreversibly. This phenomenon is known as Hayflick limit. 

C) Chronic cytotoxicity which is often a result of modulation or disruption of Ca2+ cellular homeostasis as well as the increase of reactive oxygen species in either mitochondria or any other compartment in the cell.

D) Removal of growth Factors as this normally, in many cells, leads to arrest of cell cycle followed by cell death.

A cartoon showing a comparison between necrosis and apoptosis.