Here’s how to distinguish apoptosis with necrosis?

Hello friends.

So, as I was saying in the last blog. Cell is just like us. It also tries to adapt itself to unfavourable condition with different mechanisms like being hypertrophic, hyperplastic or metaplastic etc. If you don’t know what these terms means, check out my previous blog.

If the stress gets out of control for cell… what it does? Most likely, it will die. Just like us. Wait… we don’t die? Oops, my bad!

Ok, we get it that a cell dies under stress. But the question here is not what happens, the question is how does it happen? What are the processes through which a cell death occurs? Therefore, in this article these are the questions which we will learn today.

In this article, we will learn:

  • Apoptosis
  • Necrosis

So, without any delay, let us get into play. Yes, I am very poetic.


Definition: ATP dependent programmed cell death.

Whenever, we hear cell death, it usually comes into our mind that cell death is caused by some unwelcoming causes like any injury, any trauma, any infection etc.

But, you must remember that apoptosis is not pathological always. Actually, most of the time it is needed. For eg, removal of interdigital cells for formation of fingers during embryological development. And this happens by…

Mechanism: By activated caspases (A#1) via intrinsic, extrinsic pathway. We will understand each pathway in further details.

  • Intrinsic pathway: It involves mitochondria.
    • This pathway is activated by any type of cellular injury or DNA damage.
    • Steps- Cellular injury -> inactivation of Bcl-2 (A#2) -> Cyt-C exposing from mitochondrial matrix (Q#1) into cytoplasm -> caspase activation.
  • Extrinsic pathway: It involves surface receptor-ligand and cytotoxic immune cell.
    • Here, FasL or CD95L binds with Fas or CD95 on the cell -> activating caspases. (A#3).
    • Or by cytotoxic CD8+ T-lymphoctyes mediated pathway: T-cells -> secrete perforins (glycoporteins) -> membranal pore formation -> granzymes (from CD8+ T-cells or NK cells) enter inside the cell-> activate caspases.
    • This pathway is common during viral infection or reinfection.

A#1. Caspases: Also known as by cysteine-asparate proteases.

  • Family of cytosolic proteolytic enzymes.
  • Have cysteine in their active site that dismantles the target protein at the C-terminal of aspartate acid residue in the protein.

A#2. Bcl-2: B-Cell Lymphoma 2 is a family of proteins that regulates apoptosis.

  • It does it by preventing BAX/BAK oligomerisation and making the mitochondrial membrane impermeable for the release of Cyt-C.
  • BAX and BAK are apoptosis causing proteins, member of Bcl-2 family, which are found in cytoplasm and mitochondrial outer membrane respectively.
  • BAX/BAK oligomerisation -> permeability increases (due to pore formation) of mitochondrial membrane -> release of apoptotic factors like Cyt-C from mitochondria into cytoplasm -> caspase activation -> apoptosis.

A#3. FasL: Fas ligand is a type-II transmembrane protein (protein with extracellular C end and intracellular/cytoplasmic N end) belonging to the family of TNF or tumor necrosis factor.

TNF: A cytokine (signalling protein in immune response) released by macrophages or monocytes. TNF binds to their receptor on the target cell and induces apoptosis by activating caspases.

Q#1. What is the brief structure of mitochondria?

A#1. Mitochondria are double membrane organelles, therefore having distinct compartments like outer membrane (for metabolites exchange), intermembranal space (for proton accumulation and transport during oxidative phosphorylation i.e. a step of cellular respiration for ATP production are found here), inner membrane (proteins involved with ATP synthesis), inner matrix (contains mitochondrion organelles). Outer membrane is smooth while inner membrane has folds called cristae to increase the surface area for ATP production.

Q#2. How can you distinguish apoptosis from necrosis on basis of cell morhphology during death?

A#2. Here, during cell death, its membrane will still be unscathed and without any serious inflammation.

Cytoplasm will be stained pink as of the presence of basic proteins (due to presence of basic proteins like lysine and arginin as they contain amino group) in the cytoplasm i.e. cytoplasmic components are acidophilic (acid-liking) therefore making the cytoplasm eosinophilic. Whereas the nucleus is basophilic.

Apoptosis is well recognised by presence of DNA laddering i.e. DNA fragments during karryohexis.

Q#3. How does the activating caspase leads to death?

A#3. Steps: Activated caspases -> condensing chromatin, cell shrinking, formation of blebs on membrane and apoptotic bodies -> phagocytosis.

Now, without resting, onto…


Definition: Death of tissue due to underlying pathological process.

Mechanism: Any pathology or injuries -> cell membrane destruction -> protein denaturation, cellular degradation and cellular components leaking -> inflammatory reactions (local) unlike apoptosis.

Now, necrosis has several types.

  • Liquefactive:
    • Lysosomal enzymes from neutrophils (during early inflammation) digest cells and its proteins.
    • This makes the tissue liquefactive.
    • Eg, brain infarction (microglial cells i.e. macrophage of CNS releases enzymes), bacterial infection where abscess (painful condition of pus formation due to interaction of bacteria and macrophages) is formed.
  • Coagulative:
    • Cellular shape and organ structure remains intact. However, nucleus disappears.
    • Shape is preserved due to aggregation of proteins and cytoplasm stains dark pink.
    • Eg, ischemia or infarction of any organ (except brain).
    • Here, the decreased blood supply causes injury and this destroys/denatures the enzymes. Therefore, leading to preservation of proteins as now they are not proteolysed by the enzymes.
  • Caseous: Meaning cheese like.
    • Cells are fragmented and tissue is soft like a cheese.
    • Common in TB , nocardiosis or fungal infections like histoplasmosis (A#4).
    • Involves formation of granulomas (area containing debris or pathogens like bacteria or viruses which is surrounded by immune cells such as lymphocytes and macrophages, containing the infection at a single site and preventing its outreach to other parts) during inflammation.
  • Gangrenous:
    • Can either be coagulative or liqeufactive i.e. dry or wet gangrene respectively.
    • Dry gangrene- If it occurs due to ischemia in lower limb and GI tract, it is coagulative that seems like a mummified tissue.
    • Wet gangrene- If a superinfection (infection imposing on any previously occurred infection) of the tissue occurs, it is liquefactive.
  • Fat:
    • Necrosis in fatty tissue, like in breast injury and pancreatic lipase release, where the cell’s shape is intact with vanished nuclei.
    • Occurrence of saponification– A process where fatty acids are combined with Ca2+ ions.
    • Eg, in pancreatitis, cells are damaged that release lipase enzyme extracellularly which degrades the triglycerides (as fat is present on pancreas) into fatty acids. This in turn combines with Ca2+ (Q#4) displaying a chalky-white appearance. This fat necrosis is called enzymatic fat necrosis.
    • Similarly, trauma to fatty tissue like in breast could also lead to formation of fat necrosis called nonenzymatic fat necrosis.
  • Fibrinoid: Seen with necrosis in blood vessels.
    • Occurs due to leaking of plasma proteins like fibrin (A#5) into vessels. Or seen in type III hypersensitivity reactions, more about this some other time.
    • Eg, hypertensive crisis where blood pressure is elevated that could lead to any organ damage. If it occurs during pregnancy then it could lead to preeclampsia (you can read about preeclampsia here).

A#4. Tuberculosis: A serious bacterial infection where lungs are severely affected.

  • Cause- Mycobacterium tuberculosis, a gram-positive rod-shaped bacteria.
  • Transmission- Airborne. Where tiny droplets from a sick person are released through cough or sneeze carries bacteria and inhaled by a healthy person.
  • Is either latent (inactive) or active.
  • Symptoms-
    • Cough (with blood or mucus) for more than 3 weeks.
    • Chest pain while coughing or occasionally while breathing.
    • Chills and night sweats.
    • Other general symptoms like fever, fatigue and weight loss.
  • Treatment- It can take several months to get rid of it completely.
    • Drugs like isoniazid in combination with rifampin, pyrazinamide and ethambutol are used. These drugs prevent bacterial growth.
  • As treatment is rough and takes time, it’s better to prevent before the onset of disease.
    • BCG vaccine or Bacillus Calmette–Guérin vaccine during childhood.
    • Wearing face masks.
    • Living under good ventilation condition.


  • Cause- Bacterial disease caused by Nocardia asteroides.
  • Transmission- Bacteria enters into blood stream through cut or skin wound that comes in contact with soil or water containing the bacteria.
  • Symptoms-
    • Chest pain.
    • Cough.
    • Chills and sweating.
    • Loss of appetite.
    • Unexplained weight loss.
  • Treatment: Antibiotics like sulphonamide drugs.


  • Cause- Fungal infection caused by Histoplasma capsulatum.
  • Transmission- Bacteria are found in soil, bat droppings which later is inspired with air. Therefore, people frequently going for cave expeditions are more affected.
  • Again respiratory symptoms like
    • Cough, chills, headache etc.
    • Chest pain.
    • Body ache.
  • Treatment- Antifungal drugs like itaconazole, fluconazole etc.

A#5. Fibrin: A fibrous protein involved in coagulation of blood.

Q#4. From where do the Ca2+ ions comes?

A#4. Ca2+ions could either be present due to hypercalcemic condition as seen in hyperparathyroidism, which gets deposits on any adipose tissue covered organ or in those necrosis where the tissue itself act as an accumulating point for circulating Ca2+ ions.

This was all about necrosis and apoptosis. Now, you will never get confused between these two. Also, you can answer some more questions like:

  • What are pathways that apoptosis follows?
  • What is the role of caspase enzymes?
  • How Bcl-2 work as anti-apoptotic factor?
  • Mitochondrial structure and its components role in brief.
  • Types of necrosis and characteristic features of cell/tissue/organ.
  • When a particular necrosis type could be seen?
  • And much more.

I hope you have liked it and learned a lot from it. This was a continuation of my previous article.

For next time I will write about….. uhm…. Well I don’t know. But whatever it will be, I promise it will be same as this. I mean, interesting and educational, like always. Take care.

Will see you next time.


Published by signaturedoctor

I am a doctor-to-be pursuing my medical studies. I want to share my knowledge to fellow medical students and to other interested people.

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