Necrosis and apoptosis

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Necrosis and apoptosis


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Necrosis and apoptosis

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A 55-year-old woman with a history of paroxysmal atrial fibrillation and multiple cerebrovascular accidents is found unresponsive in her apartment. Her pharmacy records showed that she did not refill her medications for the past month. On initial forensic analysis, it is suspected that she died from a stroke nearly 2 weeks ago. The family wants to determine the cause and agrees to an autopsy. If she did die from an ischemic stroke 2 weeks ago, which of the following findings are most likely to be seen on histopathology of the affected area of the brain?  


Generally speaking, cells have two ways to die. One way is by apoptosis, which is a form of programmed cell death.

The second way is by necrosis, which is when cells die due to injury or disease.

Overall, apoptosis occurs much more often than necrosis.

One example is when old skin cells undergo apoptosis, and get replaced by new skin cells.

Another example is in our hands and feet during fetal development.

Initially, human hands and feet look like duck’s feet, with webs of skin connecting the fingers.

But the cells in the webbing undergo apoptosis and that allows us to form individual digits that allow us to pick our nose and play the piano.

In contrast, necrosis occurs less frequently, and an example of that is when a blood vessel that goes to your big toe gets clogged causing ischemia, which is where oxygen and nutrients can’t reach the cells.

As a result, those cells begin to die, turning your big toe a nasty shade of black.

In apoptosis, there are two activating mechanisms - the intrinsic pathway, also called the mitochondrial pathway, and the extrinsic pathway, also called the death receptor pathway.

The intrinsic pathway occurs when a cell is exposed to stress like radiation, hypoxia, or low oxygen, a high intracellular concentration of calcium ions, or oxidative stress, which is where reactive molecules with unpaired electrons called free radicals steal electrons from nearby molecules.

These stressors cause two intracellular proteins, Bax and Bak, to move from the cytosol to the mitochondria.

Once in the mitochondria, Bax and Bak pierce the outer mitochondrial membrane making it porous and leaky.

This allows two additional proteins, called SMACS and cytochrome C, to spill into the cytosol.

SMACS binds to proteins that normally inhibit apoptosis and deactivates them.

Meanwhile, cytochrome C binds to both ATP - the main form of intracellular energy - as well an enzyme called Apaf-1.

Together, cytochrome C and Apaf-1 combine to form a large protein complex called an apoptosome.

The Apaf-1 portion of the apoptosome then cleaves an enzyme called pro-caspase 9 into its active form, caspase-9.

Caspase 9 then goes on to activate caspase-3, and caspase-3 goes on to activate other caspases - like a chain event.

Eventually this caspase cascade leads a cell to commit apoptosis.

That’s because these caspases cleave the proteins that make up the cell’s nucleus, organelles, and cytoskeleton - a bit like a ninja sabotaging a bridge by removing its nuts and bolts.

This destroys the cytoskeleton, as well as the proteins that anchor the cytoskeleton to the cell membrane.


Necrosis is a type of cell death that occurs when cells are damaged by external factors like an infection, as well as internal factors like tissue ischemia. There are six types of necrosis: coagulative and gangrenous necrosis, which happen to hypoxic tissues; liquefactive necrosis, which happens because of hydrolytic enzymes; caseous necrosis - like in tuberculosis; fat necrosis, which happens when fatty acids spill outside adipose cells, like during trauma, and finally fibrinoid necrosis - which is caused by fibrin deposits, like in malignant hypertension.

Apoptosis, on the other hand, is a programmed cell death that occurs when the body needs to get rid of damaged or unnecessary cells. Apoptosis occurs due to intrinsic and extrinsic pathways. With apoptosis, white blood cells come in and clean up the dead tissue, so this is a neat way for cells to die.


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