Necrosis – Cell Injury – General Pathology

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 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