Jun 15

Jun 15 Necrosis and Apoptosis — What Are the Differences and Their Significances?

Introduction

It is essential for the human body to safely get rid of cells, and there are many reasons why they do that. These could be due to:

Cells being senescent (old).
Cells that have finished their functions.
Replacing cells with brand new, mature and fully functioning cells.
Cells that are infected and need to be removed/eaten.
Embryogenesis where, for example, our hands were webbed; hence cells need to be removed.
Cells that are not able to carry on in a healthy manner such as the cell has been damaged beyond repair and decided to initiate cell death. This is useful to prevent cancer growths.

Apoptosis

Apoptosis comes from the Greek origin of Apo meaning “from” and Ptōsis meaning “falling”; hence describing apoptosis as “falling off”. Apoptosis describes the normal and controlled part of cell death, which plays a crucial role in the growth or development of an organism. Apoptosis has two pathways; intrinsic and extrinsic. The intrinsic pathway is also described as the mitochondrial pathway and the extrinsic pathway as the death receptor pathway.

The intrinsic pathway is initiated when the cell undergoes stress such as radiation, high calcium concentration, hypoxia, proteins being misfolded and oxidative stress. The Bcl-2 family sensors activate the Bax and Bak (two cellular proteins) which acts on the mitochondria by creating pores to release cytochrome-C and other pro-apoptotic proteins (they also deactivate proteins that inhibit apoptosis). Through a series of steps, the caspase enzymes become activated and commit the cell to go through with apoptosis. Caspase enzymes cleave vital proteins within the cell, such as cytoskeleton/organelles/nuclear membrane. The cell demonstrates these blebs formation which starts to break away from the cell. These blebs are then eaten by macrophages and are recycled.

The extrinsic pathway is initiated when macrophages recognise if a cell has completed its task, if the cell is senescent or if the cell has a pathological condition. The macrophage then initiates cell death for that particular cell. TNF-alpha, which is a signalling protein, binds to the death receptor, which is named TNF receptor 1. Through a series of steps, a multi-complex protein is created, which is named the death-inducing signalling complex (DISC). DISC activated the caspase cascade, as demonstrated earlier, causes a safe and controlled cell degradation through blebbing.

Necrosis

Necrosis comes from the Greek origin nekrōsis meaning “death” and later moved to modern Latin to necrosis. Necrosis can be described as a pathological process of cell death which could have been resulted from infections, hypoxia, trauma or toxins. Unlike apoptosis, necrosis is uncontrolled and release lots of chemicals from the dying cell to which causes damage to surrounding cells. Inflammation is often initiated due to necrosis. There are many types of morphological patterns that necrosis can present itself. These are coagulative, liquefactive, caseous, gangrenous which can be dry or wet, fat and fibrinoid.

Necrosis can start from a process called “oncosis”. Oncosis comes from the Greek origin ónkos, meaning swelling. Oncosis occurs when the mitochondria within a cell are damaged beyond recovery by toxins or hypoxia. ATP is therefore not being made which dysregulate the ionic concentration within the cell as the ionic pumps are no longer functioning. Sodium moves into the cell and water follow, making the cell explode. The content that has been released will attract immune cells which will initiate inflammation and release reactive oxygen species (ROS) and enzymes such as proteases. The surrounding tissues may be damaged, and therefore organs may fail to work.

Differences

Apoptosis

Occurs more frequently, involves one cell at a time, localised and is on purpose.
Controlled program of cell death that is normal as it is a natural physiological process.
Contains intrinsic and extrinsic pathways.
Caspase dependent pathway.
Inflammation absent.
Cell shrinks in size and the condensation of chromatin occur.
No leakage and no release of enzymes as small blebs are being released. Hence no damage to surrounding tissues.
Intact plasma membrane structure.
Eosinophilia cell-like not present (cells presenting pink on a histology slide).
Nuclear changes: fragments into nucleosome-size fragments or the nucleus usually dissolves into apoptotic bodies. Karyorrhexis and pyknosis.

Necrosis

Occurs less frequently, involves many cells, may not be localised and is pathological.
Abnormal and uncontrolled cell death that is associated with a pathological condition.
Caused by external and internal injuries.
Caspase independent pathway.
Inflammation present.
Cell swells and burst, releasing its content at once.
Swelling of the mitochondria and endoplasmic reticulum occurs.
Leakage and enzymatic digestion of neighbouring cellular contents.
Disrupted plasma membrane structure.
Eosinophilia cell-like present (cells presenting pink on a histology slide).
Nuclear changes: pyknosis, karyorrhexis and karyolysis.

Published 15th June 2020. Last reviewed 1st December 2021.

Reference

FreeMedEducation. What is Necrosis Vs What is Apoptosis? https://www.youtube.com/watch?v=1vaEVcMfa1E. Published May 27, 2018. Accessed June 5, 2020.

Kroemer G, Dallaporta B, Resche-Rigon M. The mitochondrial death/life regulator in apoptosis and necrosis. Annu Rev Psychol. 1998;60:619-642. doi: https://doi.org/10.1146/annurev.physiol.60.1.619.

Kumar, V., Abbas, A. K., Aster, J. (2014). Robbins and Cotran pathologic basis of disease. 9th ed. Philadelphia: Elsevier Saunders. Hardcover ISBN: 9780808924500.

Sandle T, Chesca A, Akhayeva AS, Marchenko AB. Apoptosis versus Necrosis. SFJ Chro Dis. 2018;1:1.