Necrosis | Cell Injury | General Pathology 🩺

Summary

This educational script delves into necrosis, a form of cell death triggered by irreversible injury. It clarifies misconceptions, distinguishing necrosis from apoptosis, and emphasizing that necrosis is always pathological. The script outlines the process involving morphological changes due to protein denaturation and enzymatic digestion, leading to plasma membrane disruption and an inflammatory response. It highlights the importance of understanding necrosis's role in tissue damage and the body's subsequent repair mechanisms.

Takeaways

• 🔍 Necrosis is a process of cell death that occurs when cells are irreversibly injured and cannot recover from the damage.
• 📌 Necrosis should not be confused with apoptosis, which is a different pathway of cell death that can be either physiological or pathological.
• 🚫 Necrosis is always pathological and results from unwanted injuries such as trauma, ischemia, toxins, or radiation.
• 🛑 The process of necrosis involves a series of morphological changes in the cell, cytoplasm, and nucleus due to irreparable damage.
• ⏳ The histological changes that characterize necrosis take a considerable amount of time, from 4 to 12 hours, to be identifiable under a light microscope.
• 💡 Necrosis is marked by the inability of the cell to carry out its metabolic pathways and generate ATP, leading to a rapid depletion of energy stores.
• 🌡 The accumulation of lactic acid due to disrupted metabolism can make the intracellular environment acidic, contributing to protein denaturation.
• 🧬 Protein denaturation within the cell leads to structural and functional disruptions, initiating morphological changes characteristic of necrosis.
• 🔪 Enzymatic digestion, both autolysis (by the cell's own enzymes) and heterolysis (by enzymes from external sources), contributes to the morphological changes seen in necrosis.
• 🩸 The disruption of the plasma membrane in necrotic cells leads to the release of intracellular contents, which can irritate and damage surrounding tissues and trigger an inflammatory response.
• 🚨 Necrosis is associated with a significant inflammatory reaction, unlike apoptosis, which does not elicit this response, making it a key distinguishing feature.

Q & A

What is necrosis?

Necrosis is a form of cell death that occurs when cells are irreversibly damaged. It involves a series of morphological changes in the cell, cytoplasm, and nucleus due to the cell's inability to recover from severe or prolonged injury.

How does necrosis differ from apoptosis?

Necrosis is an uncontrolled and pathological form of cell death due to irreversible injury, whereas apoptosis is a controlled, regulated process that can be physiological or pathological and involves the cell's systematic dismantling.

What are the common causes of necrosis?

Necrosis can be caused by trauma, ischemia, toxins, or radiation, which lead to lethal and unwanted cell injury.

What happens to the cell's energy stores during necrosis?

During necrosis, the cell cannot generate ATP, leading to a rapid depletion of energy stores as the existing ATP is quickly used up.

Why do cells undergo morphological changes during necrosis?

Morphological changes occur due to the denaturation of intracellular proteins and enzymatic digestion of the cell's components, which disrupt the cell's structure and function.

What is the role of lysosomes in necrotic cell death?

Lysosomes contain destructive enzymes that, when released due to lysosomal membrane rupture during necrosis, can digest the cell's proteins, contributing to the cell's morphological changes and death.

What is autolysis in the context of necrosis?

Autolysis refers to the digestion of a cell by its own enzymes, such as those released from lysosomes, which occurs during necrosis.

How does necrosis trigger an inflammatory response?

The disruption of the plasma membrane in necrotic cells releases intracellular contents that irritate and damage surrounding tissues, leading to an inflammatory reaction as part of the body's response to injury.

What is heterolysis in relation to necrotic cells?

Heterolysis is the digestion of necrotic cells by enzymes derived from external sources, such as white blood cells or microbes, which contribute to further morphological changes in the necrotic cells.

Why does the plasma membrane's integrity matter in necrosis?

The loss of plasma membrane integrity in necrotic cells allows intracellular constituents to leak out, which can cause further damage to surrounding cells and tissues and elicit an inflammatory response.

How does the body respond to necrotic tissue?

The body responds to necrotic tissue by initiating an inflammatory reaction that attracts white blood cells to remove dead cells and produce factors for tissue repair, potentially leading to scar formation.

Outlines

00:00

💀 Understanding Necrosis: The Basics

The script begins by introducing necrosis as a form of cell death that occurs when cells suffer irreversible injury. It emphasizes the importance of distinguishing necrosis from apoptosis, another form of cell death. Necrosis is often the result of trauma, ischemia, toxins, or radiation and is characterized by damage to body tissues. The script clarifies misconceptions about necrosis and highlights its pathological nature, in contrast to apoptosis, which can be both physiological and pathological.

05:02

🔬 The Process of Necrosis: Morphological Changes

This paragraph delves into the histological changes that occur in cells that have been lethally injured, which take 4 to 12 hours to be identifiable under a light microscope. It explains that necrosis is not merely cell injury but a series of changes in the cell's cytoplasm, nucleus, and organelles due to irreversible damage. The energy depletion in the cell leads to the accumulation of lactic acid, causing an acidic intracellular environment and biochemical changes that result in protein denaturation. These changes disrupt the cell's structure and function, leading to the morphological alterations characteristic of necrosis.

10:08

🧬 Cellular Autolysis and Enzymatic Digestion in Necrosis

The script discusses the role of enzymatic digestion in necrotic cells, where lysosomal enzymes within the cell can cause autolysis when the cell's integrity is compromised. It also explains how necrotic cells attract inflammatory cells like neutrophils and macrophages, which release destructive enzymes, leading to further morphological changes in the necrotic tissue. This process, known as heterolysis, contributes to the overall changes observed in necrosis, including the disruption of the plasma membrane and the release of intracellular contents.

15:11

🚨 Inflammatory Response to Necrosis

The final paragraph explains the inflammatory response triggered by necrosis, where the rupture of multiple plasma membranes releases enzymes and intracellular components that irritate and damage surrounding cells and tissues. This leads to vasodilation, increased microcirculation permeability, and leukocyte infiltration as part of the body's attempt to remove necrotic cells and initiate tissue repair. The script contrasts this inflammatory reaction with the absence of such a response in apoptosis, reinforcing the unique characteristics of necrotic cell death.

Keywords

💡Necrosis

Necrosis refers to a form of cell death that occurs when a cell sustains irreversible damage. It is a critical concept in the script, which differentiates necrosis from apoptosis as two distinct pathways of cell death. In the script, necrosis is described as a result of severe injury that the cell cannot recover from, leading to a series of morphological changes and eventual cell death.

💡Irreversible Injury

Irreversible injury is a condition where the damage to a cell is so severe that it cannot be repaired, leading to cell death. The script emphasizes that irreversible injury can trigger either necrosis or apoptosis, but the outcome is not the same for both. In the context of necrosis, irreversible injury results in a cascade of events that damage the cell's structure and function, ultimately causing necrosis.

💡Apoptosis

Apoptosis, also mentioned as 'apo-tosis' in the script, is a programmed form of cell death that is distinct from necrosis. While necrosis is a pathological process resulting from severe cell injury, apoptosis can be either physiological, as in the case of embryogenesis, or pathological. The script highlights the difference between these two pathways and their implications for cell death.

💡Morphological Changes

Morphological changes are the structural alterations that occur in cells as a result of lethal injury. In the script, these changes are a hallmark of necrosis and include the denaturation of intracellular proteins and the disruption of the cell's structure and function. The script describes how these changes are identified histologically in cells that have undergone necrosis.

💡Denaturation

Denaturation, as discussed in the script, is the process by which proteins lose their normal structure and function due to lethal cell injury. This process is a key factor in the morphological changes seen in necrotic cells, leading to the disruption of both structural and functional proteins within the cell.

💡Enzymatic Digestion

Enzymatic digestion is the process by which enzymes break down the components of a cell, contributing to the morphological changes seen in necrosis. The script explains that this can occur due to the release of lysosomal enzymes within the cell (autolysis) or from enzymes released by inflammatory cells or pathogens in the area (heterolysis).

💡Lysosomes

Lysosomes are organelles within the cell that contain digestive enzymes. In the context of necrosis, the script describes how lysosomes can rupture following lethal cell injury, releasing their enzymes which then contribute to the autolysis of the cell.

💡Plasma Membrane

The plasma membrane is the outer layer of the cell that controls the movement of substances in and out of the cell. The script discusses how, in necrosis, the plasma membrane becomes disrupted, allowing intracellular constituents to leak out and contribute to inflammation and further tissue damage.

💡Inflammatory Response

The inflammatory response is the body's reaction to tissue damage, which is a significant aspect of necrosis as described in the script. It involves increased blood flow and permeability, as well as the infiltration of white blood cells to the site of injury. The script contrasts this with apoptosis, where such a response does not occur.

💡Autolysis

Autolysis is a process where a cell digests itself due to the release of its own lysosomal enzymes following lethal injury. The script explains that this self-digestion contributes to the morphological changes and cell death seen in necrosis.

💡Heterolysis

Heterolysis refers to the digestion of a necrotic cell by enzymes derived from external sources, such as white blood cells or pathogens. The script describes how this process contributes to the further breakdown of the cell and the morphological changes associated with necrosis.

Highlights

Necrosis is one of the pathways for cell death when a cell is irreversibly injured.

Necrosis is not simply the removal of cells but involves a series of morphological changes in irreversibly damaged cells.

The difference between necrosis and apoptosis is that necrosis is always pathological, while apoptosis can be physiological or pathological.

Necrosis occurs due to trauma, ischemia, toxins, or radiation, and is an unwanted injury that damages body tissues.

Apoptosis is a controlled process that can be part of normal development, unlike necrosis, which is uncontrolled.

Morphological changes in necrosis take many hours to be identified histologically and are a result of severe cell damage.

Necrosis involves the cell's inability to generate ATP, leading to rapid energy depletion and metabolic pathway disruption.

The accumulation of lactic acid due to disrupted metabolism can acidify the intracellular environment in necrotic cells.

Protein denaturation within the cell leads to structural and functional disruptions, contributing to necrotic changes.

Autolysis, the digestion of a cell by its own enzymes, particularly from lysosomes, is a key process in necrosis.

Heterolysis involves the digestion of necrotic cells by enzymes from external sources like white blood cells or microbes.

The disruption of the plasma membrane in necrotic cells leads to the release of intracellular constituents, causing inflammation.

Inflammation is a response to necrosis, where the body attempts to remove dead cells and initiate repair through vasodilation and leukocyte infiltration.

Necrosis is characterized by a series of morphological changes, enzymatic digestion, and plasma membrane disruption.

The inflammatory reaction in necrosis is distinct from apoptosis, where there is no inflammation around apoptotic cells.

Necrosis involves a complex interplay of biochemical changes, protein denaturation, enzymatic digestion, and inflammatory responses.

Understanding the differences between necrosis and apoptosis is crucial for studying cell death mechanisms and their implications in disease.

The transcript provides a comprehensive explanation of necrosis, emphasizing its pathological nature and the body's response to it.

Transcripts

Right. Today we are going to talk about necrosis.

Necrosis is one of the pathways for cell death.

when the cell is irreversibly injured,

when a cell is irreversibly injured it goes through the process of necrosis

Before I explain I would love to know what is your concept of necrosis.

Yes what do you think what is necrosis?

student explaining

So he says it’s a process of getting rid of some cells.

But the thing is that you can cut my finger and get rid of some cells is it a necrotic finger then ?

No

You should cut my finger it is dead but it is not necrotic.

Right

to..For a part to be necrotic,

it should remain the part of the living organism.

So this definition is not right. What do you think, what is necrosis?

student explaining

Ok,he says necrosis is irreversible injury

but the thing is that when there is irreversible cell injury of course cell undergo death process

but some cell follow apoptotic pathway and some cell follow necrotic pathway

so it means there is a difference between necrosis and apoptosis. Both of them can occur due to irreversible injury.

Right! So it is not the proper definition

Yes, irreversible cell injury is the cause of necrosis but what is necrosis? yes!

student spesking !

without

again you repeat

Ok! Cell death with or without body needs.

I think yoou are telling me a few thinks which are very new for me.

Before I really ask you more I think I should really what is necrosis

Right! Let me tell you when a cell is irreversibly damaged

first of all if cell is going to die right usually it follows one of the two pathways

if a cell is going to die the cell death normally follows one of the two pathways

either it goes to the pasthway of necrosis or it goes through the pathway of apoptosis.

right !

It is called apoptosis it is also called as apo-tosis. P is silent

when a cell is going to die right

Either it goes through necrotic process or apoptotic process or apo-tosis

is that right!

but these are two very different pathways

Necrosis always occurs when there is irreversible cell injury right?

When there is irreversible cell injury

lethal cell injury and unwanted cell injury.

Accidental cell injury pathological cell injury

Necrosis maybe due to trauma, maybe due szcemia, maybe due to toxins, maybe due to radiation.

So whenever necrosis occurs in your body it is usually a result of unwanted injury

and it always damages the body tissues .

Apo-tosis it maybe physiological or it maybe be pathological.

Sometimes pathologically we want some cell to be removed from our body.

For example during embryogenesis right some cell should disappear by the process of apoptosis.

Right! So apoptosis cane physiological or can be pathological

Necrosis is always pathological.

is that Right!

This is very important . So just saying ever cell death is necrosis is not true.

Is that right? You must be very clear what is necrosis

and let me tell you what is necrosis. Necrosis is basically a series of morphological changes.

what is necrosis?

it is a series of morphological changes...morphological changes.

in the lethaly injerd cell

In a lethally injured or irreversibly injured cells.

it means when a cell is so severely damaged. Right! If a cell is so severely damaged

that it cannot adapt to the injury, it cannot reverse its damage,

it cannot adjust with the stress of injury.

Right! Cell cannot recover due to sever injury or prolonged injury.

Right! Then certain changes come into a cell. Those changes which come they take many hours.

Those histological changes which appear in a, in a lethally injured cell,

those changes take many hours they take 4 to 12 hours to be identified histologically.

To be identified those changes with light microscope.

Those series of changes that occur to a lethally injured cell. Those changes are called necrosis.

just cell injury is not necrosis. Cell injury maybe reversible or it maybe irreversible.

Cell injury may lead to necrosis or may lead to apoptosis.

So what is necrosis?Necrosis is a series of changes occurring in a cell

cytoplasm and nucleus and other organelles when cells irreversibly injured .

So the whole lecture about the concept of necrosis should be

that when we are studying necrosis we have to talk about what are changes occurring in cell

which have been injured. It means when a cells lethally injured

just imagine. Just imagine there is a cell here,

Right! happy cell and unfortunately some very sever injury occurs to it.

Right! Now, after the it will pass through certain changes,

it will pass through certain changes and those changes will eventually lead to the death of cell

these changes are called necrosis.

Right! these changes are, these series of changes which occour in a cell which is lithelly injurd

is called necrosis.

am I clear....now

lets develop this basic concept

why these changes occur?

when a cell is lethally injurd why cell undergoes changes?

I will tell those changes in detail.

The reason is that when cell is lethally injured

it cannot run its metabolic pathways it cannot generate its ATP so whatever ATP

or whatever energy currency is present in the cell that is rapidly utilized, that is rapidly utilized.

. So then very rapidly energy stores go down.

In the injured cell, severely injured cells energy stores go down

and as you know just one of the example

you convert glucose to pyruvic acid and then normally it enters into Kreb cycle.

By use of oxygen if cell cannot run this mechanism its so severely injured

pyruvic acid will convert into lactic acid.

And as lactic acid accumulate into cell it will intracellular environment very acidic,

it will intracellular environment very acidic.

And there will be more biochemical changes as well not only this.

So all these biochemical changes in a severely injured cell or lethally injured cell denature the proteins

which are present in the cell

so those protein denaturation start changes into cell

when there is lethal injury intracellular protein undergo denaturation

and when those intracellular proteins are undergoing denaturation right?

That will lead to certain changes into cell structure and function

so what really happens as I said these morphological changes

The stress in on changes. Morphological changes in a lethally injured cell.

and These changes are due , yes these changes are due yes no.1 yes intracellular proteins denaturation.

Right! And as you know the cell has mainly two categories of protein. Mainly two types of protein.

. It has structural protein when they are denatured structure of the cell will be disrupted.

structure of the cell will be disrupted.

and there are functional proteins.

Structural proteins and there are functional proteins.

Functional proteins are enzymes and there are pumps in the cell

and there are regulatory proteins they are also denatured

and if these intracellular proteiins are denatured naturally function and structure of the cell is disrupted.

Is that right? And this will translate into morphological changes into cell.

Is that right then the first thing was lethal injury irreversible injury,

sever injury to the cell leading to certain morphological changes.

Why these morphological changes are occurring? No 1 due to protein denaturation.

And secondly there is an enzymatic digestion of such severely injured cells.

Right! And there is enzymatic digestion of severely injured cells.

Right! These enzymes will digest the cell they also bring morphological changes.

Is that right? So why the morphological changes are there In the necrotic tissue?

Yes why the morphological changes in the necrotic tissue?

Number one due to denaturation of proteins and

number two due to enzymatic digestion of injured, lethally injured cells.

Is that right? Now, enzymatic digestion why?

The reason being that cell, most of the cells have lysosomes Right? and other enzymes,

the destructive enzymes and those lysosomes lets suppose this enzyme has lysosome,

lysosome enzyme are limited within the lysosomal membranes

but when the cell is injured lysosomes may burst

and if lysosomes burst then what will happen that these enzymes will come out

out and start damaging the intracellular proteins.

Right! And if they start digesting the protein of course there will be again morphological changes

due to proteolysis of cellular component or digestion of cellular component.

So this will bring more morphological changes.

. So this digestion of lethally injured cell due enzymes which are present within the cell

like enzymes of lysosomes

If this is going on such type of digestion of cell by its own enzymes is called autolysis.

it is called autolysis.

But as we will see necrotic cells also attract the neutrophils, macrophages and other inflammatory cells.

And when these inflammatory cells come to the injured area these inflammatory cells also release

destructive enzymes

or necrotic area there maybe pathogenic bacteria

and if those bacteria are there that bacteria may also release destructive enzymes.

And those destructive enzymes either by the incoming or accumulating neutrophils

or by the proliferating microbe

these enzymes from leukocyte sources and microbial sources also do further digestion of the cells

so it means they do further morphological changes into lethally injured cell.

Is that right? So if this type of digestion is going on.

Right, from those enzymes which are not from the necrotic cell itself

but enzymes which do digestion and this enzyme digestion.

For example this is a neutrophil and this is releasing enzyme

or here’s a microbe it is also releasing destructive enzyme.

Now this is not autolysis this is called heterolysis

so if necrotic cell is undergoing injury, digestion due to its own enzyme, it is autolysis.

If it is undergoing what? Digestion due enzyme derived extrinsic to this cell either from the white blood cell

or from the

microbes then we say heterolysis.

So what did we learn up to now?

That in cells what is necrosis? It is series of morphological changes

occurring in a lethally injured cell and these changes are induced by denaturation of intracellular proteins

and by enzymatic digestion of lethally injured cells.

. Am I clear? Secondly a very big hallmark of necrosis is that

plasma membrane of the cell is disrupted. Plasma membrane of the cell is disrupted

and if plasma membrane of the cell is disrupted then intracellular constituents come out,

intracellular constituents come out. Cell start bleeding in a way.

. Of course there is no blood in the cell I am just saying that what will happens

when cells are lethally injured they are unable to maintain the integrity of their plasma membranes

so when plasma membranes become disrupted at multiple level intracellular substances come into

extracellular area or surrounding interstatium and intracellular lysosomes are being ruptured

so dangerous compound come out. Dangerous proteolytic enzyme or destructive enzymes are released.

So if there are 40 cells which undergo necrosis

and when there cell membranes are disrupted they are releasing what? Injurious enzymes

and intracellular components and these components when they leak out,

right! Intracellular material leak out. It irritates and injury they surrounding cell and surrounding tissue

and you know when ever a tissue is injured there is inflammatory reaction

because remember necrosis does not occur in one cell.

Apoptosis can occur in one cell or very small cluster of cell.

Necrosis is usually in larger group of cells right. So when a group of cells is undergoing necrosis,lethal injury

there cell membranes are not well maintained and from this disrupted cell membranes lot of enzymes are

coming out

and when intracellular components are leaking out and they injure the surrounding area, cells and elicit at the

inflammatory response.

The surrounding cells you know the chemical mediators will be generated at this site and there will be vasodilatation.

And increase permeability in microcirculation and leukocyte will start infiltrating.

Why this is happening? Because when inflammatory reaction will occur in the surrounding area,

when inflammatory reaction will occur the white blood cells will come out,

they will try to eat the necrotic cell and try to induce the repair.

You understand it? Necrotic cell should not stay forever in the body

so our body how it would respond that whenever a group of cell undergoes necrosis

these cells themselves produce chemical substances

elicit or initiate the inflammatory reaction against the around the necrotic zone

and as a part of that inflammatory reaction blood vessels that surround that tissue undergo vasodilation

and microcirculation undergo increased permeability then proteins antibodies and white blood cells

they leak out into the necrotic area and then ofcourse as time passes by these neutrophils or macrophages

they will start eating the necrotic cell and while they are removing the dead cell

they produce the factors

which will lead to proliferation of local cells so that tissue can be repaired

is that right ?

or even activate the fibrosite into fibroplast and collagenization or scar formation can occur.

Am I clear? This is very important to remember

such inflammatory reaction does not occur in apoptosis

this does not occur in apoptosis, around apoptotic cell,

it’s a classical feature of necrotic cell. Am I clear?

Any question up to this so now we can say that there is more morphological changes occur.

Number one morphological changes occur due to protein denaturation secondly it occur due to

enzymatic digestion

thirdly morphological changes into necrotic cell around its tissue occur

due to loss of integrity of, integrity of yes, plasma membrane of necrotic cells.

Right membrane rupture at multiple points, remember apoptosis membrane make blabs

but does not rupture.in necrotic cells cell membrane rupture and from the ruptured cell membrane.

Right, the components which come out they elicit intracellular component leak out and they elicit.

Yes, inflammation. Inflammation. Right! So inflammation is also a part of the necrotic reaction.

Right! So now I will just sum up and then we will move forward. What is necrosis?

Now next time you don’t give me funny answers

Its very clear necrosis is a series of morphological changes

due to, number one due to intracellular protein denaturation,

no. 2 these changes are due to enzymic digestion and number three due to disruption of,

disruption of plasma membrane and intracellular components come out and elicit inflammatory reaction

all these changes are components where as all these are happening where a cell

and if many cells of course in necrosis you need many cells necrotic tissue is undergoing morphological changes.

now first of all...