Right, today we are going to talk about necrosis. Necrosis is one of the pathway for the cell death. When a cell is irreversibly injured, it goes through the process of necrosis.
Before I explain to you, I would love to know what is your concept of necrosis. Yes, what do you think? What is necrosis? 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! If you cut my finger, it is dead.
But it is not necrotic. Right? 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 of? What is necrosis? Irreversible cell injury. Okay, he says necrosis means irreversible cell injury.
But the thing is that when there is irreversible cell injury, of course cell undergo death process, but cell... some cells follow apoptotic pathway and other cells follow necrotic pathway so it means there is difference in necrosis and apoptosis both of them can occur due to irreversible cell injury right so it is not the proper definition yes irreversible cell injury is the cause of necrosis but what is necrosis yes without body heat Cell death with or without body needs. I think you are telling me few things which are very new for me.
Before I really ask you guys more, I should tell you really what is necrosis. Let me tell you. When a cell is irreversible, First of all, if cell is going to die, 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.
pathways either it goes to the pathway of necrosis or it goes to the pathway of apoptosis right it is called apoptosis it is also called apoptosis be silent when a cell is going to die right either it goes through necrotic process or it goes through apoptotic process or apoptosis is that right but these are two very different pathways necrosis always you occur 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 may be due to trauma may be due to severe ischemia may be due to toxins may be due to radiation so whenever necrosis occurs in your body it is usually a result of of unwanted injury and it always damages the body tissue. Apoptosis, it may be physiological or it may be pathological. Sometimes physiologically we want some cell to be removed from our body. body for example during embryogenesis right some cells should disappear so they disappear by the process of apoptosis right so apoptosis can be physiological and or can be pathological necrosis is always pathological is that right this is very important so just saying every cell that says necrosis is not true You must be very clear what is necrosis. Let me tell you what is necrosis.
Necrosis is basically a series of morphological changes. What is necrosis? It's a series of morphological changes in a lethally injured cell. In a lethally injured cell.
In a lethally 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 severe 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 lethally injured cell, those changes take many hours, 4 to 12 hours to be identified histologically. To be identified those changes with light microscope Those series of changes which occur to a Lethally injured cell Those changes are called necrosis Just cell injury is not necrosis Cell injury may be reversible or it may be 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 cell is irreversibly injured. So the whole lecture about concept of necrosis should be that when we are studying necrosis we have to talk about what are the changes occurring in the cell which has been injured.
It means when a cell is lethally injured, just imagine there is a cell here, right? Happy cell and unfortunately some very severe injury occurs to it. Now, after the injury it will pass through certain changes.
It will pass through certain changes. changes and those changes right will eventually lead to the death of cell these changes are called necrosis right these changes are the series of changes which occur in a cell which is neatly injured is called necrosis am i clear now let's develop basic concept why these changes occur When a cell is lethally injured, 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 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 cells, severely injured cells, energy stores go down. And as you know, just one of the examples, as you glucose, you convert glucose into pyruvic acid and then normally it enters into the Krebs cycle by use of oxygen.
If cell cannot run this mechanism, it is so severely injured, pyruvic acid will convert into lactic acid. And if lactic acid accumulates into cell, it will make intracellular environment very acidic. It will make the intracellular environment very acidic.
And there will be more biochemical changes as well, not only this. So all these biochemical changes in the severely injured cell, or the legally 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 proteins undergo denaturation and when those intracellular proteins are undergoing denaturation, right?
that will lead to certain changes into cellular structure and function so what really happens as I said these are morphological changes the stress is on changes morphological changes in a lethally injured cell and these changes are due to yes they are due to number one yes intracellular proteins denaturation Right? And as you know the cell has mainly two categories of proteins, two types of proteins. They are structural proteins. 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 proteins are denatured, naturally structure and function of the cell is disrupted. Is that right?
And this will translate into morphological changes into cell. Is that right? Then, so first thing was lethal injury, irreversible injury, severe injury to the cell leading to sudden Why these morphological changes are occurring? Number one, due to protein denaturation and secondly, there is 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 are there in necrotic tissue? Number one, due to denaturation of proteins. And number two, due to enzymatic digestion of lethally injured cells.
Is that right? Now, Zymatic digestion why? The reason being that cells, most of the cells have lysosomes and other enzymes, destructive enzymes and those lysosomes, lets suppose this enzyme has lysosome, lysosomal enzymes are limited. within the lysosomal membranes but when cell is injured lysosomes may burst and if lysosomes burst then what will happen that these enzymes will come out and start damaging the cellular proteins right and if they start digesting the proteins of course there will be again morphological changes due to proteolysis of cellular component digestion of cellular components so this will bring more morphological changes now this digestion of lethally injured cell can occur due to enzymes which are present within the cell like enzymes of lysosome 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 in necrotic area there may be pathogenic bacteria and if those bacteria are there, those bacteria may also release destructive enzymes and those destructive enzymes either by the incoming or accumulating neurons 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 cells Is that right? So if this type of digestion is going on from those enzymes which are not from the necrotic cells itself but enzymes which do digestion and this enzyme digestion for example this is a neutrophil and this is releasing enzyme or here the 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. But if it is going under what? Digestion due to enzyme derived extrinsic to the cell either from the white blood cells or from the? microbes then we say heterolysis. So what did we learn up to now?
That in cells, what is necrosis? It's a series of morphological changes occurring in a lethally injured cell and these changes are induced by denaturation of intracellular proteins and bioenzymatic 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. Cells start bleeding in a way.
Of course there is no blood in the cells. I am just saying The saying that what really 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 levels, intracellular subsets are destroyed.
substances come into extracellular area or surrounding interstitium and intracellular lysosomes are being ruptured so dangerous compounds come out dangerous proteolytic enzymes or destructive enzymes are released so if there are 40 cells which undergo necrosis and when their 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 irritate and injure the surrounding cells and surrounding tissue and you know whenever 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 usually in a larger group of cells, right? So when a group of cell is undergoing lethal injury, their cell membranes are not maintained well and from this disrupted cell membranes, lot of enzymes are coming out and intercellular components are leaking out and they injure the surrounding cells and elicit the inflammatory response. The surrounding cells, you know, chemical mediators will be generated at the site and there will be vasodilatation and increased permeability in microcell. and leukocytes will start infiltrating.
Why this is happening? Because when inflammatory reaction will occur in the surrounding area when inflammatory reaction will occur, then white blood cells will come out, they will try to eat the necrotic cells and try to induce the repair You understand it? Necrotic cells should not stay forever in the body.
So our body, how it responds? That whenever a group of cells undergoes necrosis, these cells themselves produce chemical substances which elicit or initiate the inflammatory reaction. against the around the necrotic zone and as a part of that inflammatory reaction gut vessels around that tissue undergo vasodilation and microcirculation undergo increased permeability then proteins antibodies and white blood cells they leak out into necrotic area and then of course as time passes by these neutrophils the macrophages they will start eating the necrotic cells and while they are removing the dead cells 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 fibrocyte into fibroblast and collagenization of 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 around apoptotic cell. This is a classical feature of necrotic cell. Am I clear?
Any question upto this? So now we can say that there is more morphological changes occur number one morphological changes occur due to protein denaturation secondly it occurred due to enzymatic digestion thirdly morphological changes into necrotic cells and 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 in apoptosis membrane make blebs but does not rupture. In necrotic cells, cell membranes 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 part of the necrotic reaction right so now I will just sum up and then we'll move forward what is necrosis now next time you don't give me funny answers it's very clear necrosis is a series of morphological changes occurring in a lethally injured cells and these changes are due to number one due to intracellular protein denaturation number two this changes are due to enzyme digestion and number three due Due to disruption of plasma membrane and intracellular component come out and elicit inflammatory reaction. All these changes are the component where all these are happening when a cell and if many cells of course in necrosis usually there are many cells necrotic tissue is undergoing morphological changes.
Now first of all