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 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 uh 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 to for a part to be necrotic it should remain the part of the living organism so this definition is not right what what do you think of what is necrosis okay he says necrosis mean irreversible Sal injury but the thing is that when there is irreversible cell injury of course cell undergo death process but some cell follow apototic pathway and other self follow necrotic pathway so it means there is a difference in necrosis and apoptosis both of them can occur due to irreversible cell injury right so it is not the proper definition uh yes irreversible cell injury is the cause of necrosis but what is necrosis yes without it again you repeat that okay sell that with or without body needs I think you are telling me so few things which are very uh new for me before I really ask you guys more I should tell you really what is the process right let me tell you when a cell is irreversibly damaged first of all a 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 pathway of necrosis or it goes through the pathway of apoptosis right it is called apoptosis it is also called apoptosis P silent when a cell is going to die right either it goes through necrotic process or it goes through a poptartic process or apoptosis is that right but these are two very different pathways necrosis always occur when there is irreversible cell injury right when there is irreversible cell injury injury and unwanted cell injury accidental salary pathological challenges necrosis may be due to trauma maybe due to severe ischemia maybe due to toxins maybe due to radiation so whenever the crosses occurs in your body it is usually a result 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 for example during embryogenesis right some cells should disappear so they disappear by the process of apoptosis right so apoptosis can be physiological or can be pathological necrosis is always pathology is that right this is very important so just saying every cell death says necrosis is not true the night 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's a series of morphological changes morphological changes in a literally injured cell you know literally 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 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 literally injured cell those changes take many over 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 a necrosis cell injury may be reversible or it may be reversible 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 just imagine there is a cell here right happy cell and unfortunately some very severe engineer comes to it right now after the injury it will pass through certain changes it will pass through certain 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 Loosely injured is called necrosis now let's develop basic concept why these changes occur when a cell is literally injured why is 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 and the injured cells will lead yourself energy stores go down and as you know just one of the example as your glucose you convert glucose into pyruvic acid and then normally it enters into Krebs cycle by use of oxygen if Cell cannot run this mechanism software Ranger pyruvic acid will convert into lactic acid and if lactic acid accumulate into Cellar it will make intracellular environment very acidic it will make intracellular environment going yesterday and there will be more biochemical changes as well not only this so all these but changes in the severely injured cell or lethally injured cell denature the proteins which are present in the cell so those protein denaturation star changes into cell when there's lethal injury intracellular protein is 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 import 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 intra cellular 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 this 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 injuries leading to certain morphological changes 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 swear linger cell 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 nephrotic in necrotic tissue number one due to naturalized denaturation of proteins and number two due to enzymatic digestion are injured listening yourself is that right no enzymatic digestion why the reason being that felt most of the cells have lysosomes right and other enzyme destructive enzymes and those lysosomes let's suppose this enzyme has lysosome lysosomal enzymes are limited within the lysosomal membrane but when cell is injured lysosomes will be 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 they 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 atolysis it is called Auto license 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 the crotic 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 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 lethal injured cells is that right so if this type of digestion is going on right 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 neutrophila and this is released in enzymes or here's the microbe it is also releasing destructive endile now this is not auto license this is called heterolysis so if necrotic cell is undergoing injury digestion due to its own enzyme it is auto license but if if it is going uh 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 lithium injured cells secondly a very big Hallmark of necrosis is that plasma membrane of the cell is disrupted plasma membrane of the cell is disrupted and a plasma membrane of the cell is disrupted then intracellular constituents come out constituents come out self start building in a way of course there's no blood in the cells I'm just saying that what really happens when cells are literally 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 and intracellular lysosomes are being ruptured so dangerous compounds come how dangerous proteolytic enzymes 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 cellular components and these components when they leak out right intracellular material leak out it irritates and injure the surrounding cells and surrounding tissue and you know whenever our 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 Julian a larger group of cells right so when a group of cell is undergoing the lethal injury their cell membranes are not maintained well and from this disrupted cell membranes lot of enzymes are coming out and intracellular components are leaking out and they injure the surrounding a cells and allocate the inflammatory response their surrounding cells you know chemical mediators will be generated at the site and there will be visa dilatation and increase permeability in micro circulation and leukocyte will start infiltrating why this is happening because when inflammatories 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 respond that whenever a group of cylindrical necrosis these cells themselves produce chemical substances which elicit or initiates the inflammatory reaction against the around the necrotic Zone and as a part of that inflammatory reaction that vessels around that tissue undergo visualization and micro circulation 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 fibroblasts 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 apototic cell it's a classical feature of 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 according 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 Point remember in apoptosis membrane make blabs but does not rupture in necrotic cells cell cell membranes rupture and from the ruptured cell membrane right the components which come out they illicit intracellular component leak out and they illustrate yes inflammation inflow mission right so information is also a 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 literally injured cells and these changes are due to number one due to intracellular protein denaturation number two this changes are due to enzyme it digestion and number three due to disruption of disruption of plasma membrane and intracellular component come out and LSA inflammatory reaction all these changes are the component where all these are happening when a cell and if many cells of course intercourages usually there are many cells in a necrotic tissue is undergoing morphological changes now first of all now as we discussed that necrosis basically changes occurring in a lithium now these changes do not occur suddenly these changes which uh that is denaturation of proteins enzymatic digestion and inflammatory reaction these changes take many hours depending upon the tissue and depending upon the cause of the injury these changes take many hours four to usually 4 to 12 hours are required before these changes in necrotic changes can be manifested under the light microscope is that right and very importantly it's very important that if person dies if a person organism dies before much earlier then the tissue will not show necrotic changes let me give you a classical example let's suppose we talk about myocardial infarction and I will explain that what is the importance of timeline let's suppose here is your heart I'm making a very simple diagram right and here is the blood vessel which is supplying this part of the heart right and this blood vessel is closed let's suppose that here is uh atherosclerotic plaque and this plug suddenly is disrupted or a thrombus form on it and this is closed if the what will happen then on the dependent myocardium there are the severe ischemia or hypoxia there will be sphere deficiency of oxygen and other nutrients to the dependent myocardium let's suppose this is the dependent myocardium right this piece of myocardium is now if if severe deficiency of oxygen and nutrients remain more than 30 minutes it is irreversibly injured it is irreversibly injured but if person dies let's suppose if person dies within one hour for example in sudden cardiac death person dies within one hour of onset of these symptoms and after the death if you remove the heart and you try to look the area of necrosis will you find morphological changes of necrosis answer is no very good if person dies Within one or two hours for example in certain cardiac death after the onset of severe ischemia to a part of myocardium right necrotic changes will not be there let's suppose I give an example for our example person dies after three hours of onset of swear chest pain now cause of death may be that uh this ischemic area precipitated ventricular tachycardia or ventricular fibrillation right due to techyarhemia person dies if this person dies even though there has been severe injury irreversible injury lethal injury to these myocardial cells but if after two hour or three hour you look under the microscope these cells they will not show necrotic changes because it takes many hours amateur then in such person who had developed very severe myocardial ischemia which is leading to myocardial severe dysfunction or precipitation of dangerous arrhythmias and person dies earlier you will not find necrotic changes or changes of necrosis what you may find you may find evidence of chronic chronic atherosclerotic disease of coronary arteries or you may find evidence of plaque plaque disruption through arthromatous plaque disruption or you may find some evidence of remote myocardial infarctions and their healed scarf listen carefully again what I'm trying to put in your mind I'm trying to put that when a reversible when severe lethal injury occur necrotic changes don't appear like this they don't appear like this they take long time and during those hours that that inter tissue should remain the part of the living organism if organism dies very early then tissue was not alive for a long time to produce necrotic changes my morphological changes in the injured cells am I clear what happens in these cases if early death occur right you may not find the crotic astrological changes into myocardial cells but as I told you one of the Hallmark of negrosis is plasma membrane cell membrane disruption right when myocardial cells are disrupted and myocardial cells are disrupted intracellular cardiac specific enzymes and proteins May leak out from severely injured area because membranes or cells are disrupted those proteins and those enzymes which are cardiac specific which are specially present in myocardial cells the common membranes are ruptured they leak out into interstitution and drain through lymphatics and capillaries into the general circulation right and such enzymes can be detected in the blood blood of the patient as early as two hours of that for example there can be cardiac specific troponin t or cardiac specific troponin eye right these are calcium binding proteins right this is a special type of calcium binding proteins right which are present in myocardial cells and when they are injured they leak into blood or there is a creatinine kinase enzyme which was present in many tissues one of its special type which is called ckmv myocardium bound specifically especially present in myocardium in a higher concentration so this will also leak into blood so what will happen that if someone suffers with severe injury ischemic injury to the myocardial cells lethal injury irreversible injury of course these cells start the process of necrosis but it is going to take many many hours is that right and if you want to make a diagnosis of course you make with the symptom of what is this myocardial infarction ECG also help plus you look for the biomarkers of myocardial infarction in the blood is that right so if a patient with sweet chest injury has in the blood troponins High concentration ckmp High concentration right you know that irreversible damage has been done to the part of myocardial cells but if this cells remain there and patient remain alive what what will happen these cells will produce chemical mediators of inflammation around it inflammatory reaction will occur what will happen inflammatory reaction will occur and from the inflammatory Zone neutrophils and macro first neutrophil will arrive there and later on macrophages will arrive there and what they will do over that days they will start digesting away the necrotic cells and start activating the localized fibroblast converting the fibroblast into sorry converting localized fibrocytes local fibrocytes activating the fibrocytes and activated fibrocytes are called fibro glass and those fibroblasts start producing collagen and over some week eventually this necrotic cells will disappear and collagen collagen will be deposited in that area right a scar will be formed in The myocardium yes right done now let's come back I initially I told you I will keep on stressing morphological changes it means what are these morphological changes even though I told it is these morphological changes are due to denaturation of proteins it is due to enzymatic digestion and it is also there is an inflammatory reaction but first we talk about single cell let's suppose report uh I will put one single cell and I will show you what changes according to that cell right when it is irreversibly injured of course changes can occur into cell membranes changes can occur into cytoplasm changes can occur into cytoplasmic organelles and changes can occur into nuclear material is that right now let's suppose this is our normal cell right and I will compare it with the necrotic cell this is a normal cell let's suppose here it is having a nucleus right and you know normally the cytoplasm takes which color synophilic right cytoplasm takes cytoplasmic protein take acinophilic color right cytoplasmic proteins right they bind with stain yourself the xenophilic color is slightly pinkish so what happened and cytoplasm does have what ribosomes but ribosomes take which color blue color they bind ribosomes like nucleic acids RNA does not bind the use in that binds hematoxylin which gives a blue color as plasma proteins are more and ribosomes are less so there's more normally the more xenophilia and less because of India in the cytoplasm is that right and of course nucleus has a lot of DNA and it binds lot of hematoxylin so it is deeply deeply which color basophilia there's opium in blue color hematoxylene blue color it binds with RNA DNA classically and eosin pink color reddish color and due to because it binds with the plasma protein specific sorry a cellular proteins am I clear now and of course there are organelles also there is let's suppose Mito country and further detail I will not go now when a cell is literally injured what happens to the cell here is the injury right lethal injury What will what will be the changes which will occur in the cell number one protein denaturation process will start right these changes we can see under light microscope when protein denaturation will start just imagine this is protein a folded protein and it will open up when it opens it binds more stain is that right when proteins is tightly folded it binds less your sin and when they denature and open up at multiple points your skin buying so cell cytoplasm will become intensely a synophilic cell which is having denatured proteins unfolded proteins they tend to bind more in your sin so cell becomes cytoplasm become more intensely a synonym more reddish is that right and here is the cell now nuclear changes I will talk later right they occur simultaneously but I will talk later now what happened cell become more intensely the question is that why cell becomes so intensely xenophilic the two explanation number one add protein is undergo denature maturation denatured proteins is your sin so it becomes more intensely red number two you know ribosomes they bind which color blue color hematoxylin they also undergo disintegration and ribosomes disappear during the necrotic process when they disappear there is loss of basophilia cytoplasmic basophilia the loss of cytoplasmic basophilia due to disintegration of ribosome so double reason why it become more pink one reason loss of blue coloration which is little bit normally present and number two increase standing by the eosin so these two reasons lead to xenophilia so what we can say in a necrotic cell a process passes by number one change which I told you what is that cytoplasm become more a synophilus clear then another thing over the time of course I told you that there are what organelles there they are different mitochondria or lysosomes and other as time passes by even these organelles right they are also digested away when they will become digested away what will happen to the cell I will talk about nuclear changes later right I'm just talking about cytoplasmic changes now the cell will become remain what is this highly sin of a lake right and okay one more point before I talk about original one more point I would love to mention that is that cells have granules of glycogen as stored energy what is this granules of glycogen actually when cells undergo extreme stress they convert glucose into pyruvic acid and lactic acid so it is partial breakdown of glucose so it is not energy efficient under this stress cells very rapidly break down glycogen into glucose and consume it so glycogen granules also disappear if glycogen granules disappear it means on staining the granular appearance of cytoplasm will be lost and cell will become homogeneous glassy it will become homogenous glossy so number one change was increased because you know philia in cytoplasm right number two due to loss of glycogen granules what will happen there is a cell become more homogeneous and glassy appearance glassy appearance of the cytoplasm more homogeneous classy appearance due to loss of grand granularity which is normally imparted by glycogen granules which are rapidly consumed Third change not only they become intensely pink and glossy cytoplasm but at multiple points when these organelles are digested away then these areas will look empty spaces they will look as empty spaces and these empty spaces it looks as if some moth caterpillar moth has eaten the cell so it gives more eaten appearance moth eaten it is not a mouth eaten that is somewhat I think romantic situation it's moth moth is something like Caterpillar right related with the what is that insects with two big Broad it's not butterfly it's slightly different or maybe I don't know I'm not specialist in in sex but I know moth is something like insect with a very big broad wings too right so anyway their caterpillar it appears as if moth has eaten multiple points is that right these are the cytoplasmic changes I will repeat it when cell is undergoing changes number one there is increase is xenophilia number two there is glassy appearance xenophilia due to increase protein denaturation binding more eosin and loss of basophilia due to loss of ribosomes glossy appearance has loss of granularity in the cell which was produced by the glycogen right and thirdly as organelles disappear right those areas look empty spaces as if they are not eaten appearance I'm going to tell you after that I will tell you what are myelin figures okay ah so now she'll want to know what a myelin figure let me tell you when sell most of the components are digested away and sells most of the components are digested away then cell membranes may be left over there when enzymes do proteolysis proteinaceous substances digested away then cell membranes or organelles membrane let's suppose this is cell membrane and organ of the membranes they are dumped they are left at the site of necrosis and usually they are like world you know they look like this world phospholipid masses these are just crumpled membranes these are called myelin figures these are called myelin figures these are called Milan figures two things happen to these myelin figures either macrophages come and they they heat up the phagocytosma myelin figures and they disappear or if they stay in the body for very long time in the living organism ideally what should happen the macrophages which come they should eat up the cellular debris and cellular component and eventually they should eat up myelin figures although which are more resistant to digestion phospholipid membranes world pieces of phospholipid membranes but if they stay there and they have not been phagocytosis then phospholipids are negatively charged so they will attract the calcium they will attract the calcium so calcium will bind there and when calcium will bind there then this part of the cell will undergo dystrophic calcification dystrophic calcification the classical example is in tuberculosis patient when there is cases necrosis KCs tissue stays in the body for longer time because macrophage cannot effectively remove it so then KCs tissue which has lot of having lot of lipids right these cases tissue May undergo calcifications so in many situations if necrotic cells persist in the body for longer time right then that will lead to what changes calcification of those cells or calcification of remaining mitochondria or calcifications of remaining myelin figures am I clear right so these are light microscopic changes in a necrotic cell now we come to electron microscopic changes if you that is called Ultra structural changes under the electron microscope what changes you will find in these cells number one plasma membrane rupture right plasma membrane ruptures or discontinuities in the plasma membrane discontinuities in plasma membrane and these ruptures are not only into cell plasma membrane but also these ruptures under electron microscopic can be visible in organelles membrane right then not only plasma membrane structure is there of course you will find under electron microscope that injured mitochondria swella right this is normal mitochondria right and injured mitochondria become swollen and with those these mitochondria Also may have dense amorphous bodies dense amorphous body this is a feature of severe injury to Mito chondria that mitochondrial enzymes structures plump so what do you see under the electron microscope when cells are passing through necrotic changes of course plasma membrane structures are there or discontinuities are there in the cell as well as intracellular organelles secondly mitochondrial enlargement mitochondrial enlargement swelling and large amorphous densities present in the Mito chondria large amorphous density is present in the mitochondria with that intracellular organelles their membranes they may be seen like small what are these myelin figure so small but multiple myelin figures within the necrotic cell these are derived when different lysosomal or peroxisomes or Golgi operators or endoplasmic reticulum are mitochondria all those membranous organelles undergo what changes right and they may end up with small intracellular multiple myelin figures is that right then within the cell there may be in the cytoplasm although there may be some amorphous deposits right these may be denatured proteins amorphous fluffy material may be present in cytoplasm of a necrotic cell which can be visualized by the electron microscope what it is it is necrotic in the necrotic cell it is denatured proteins these are denatured proteins right so you can see under electron microscope the changes which you will see we call them Ultra structural changes and these changes may be ruptured membrane swollen mitochondria amorphous densities multiple intracellular myelin figures and fluffy amorphous deposits in the cytoplasm which may be representing uh denatured proteins is that right so these were the changes in the cells now we come to the changes in nucleus that what happens to these nuclei of lethally injured cells right this nuclei can disappear because as proteins are being digested in the same way and enzymes may lead to digestion of nucleic acids they may digest DNA they digest RNA another component of nucleus so this nucleus also eventually disappear but in different cells it disappears by different style it is its disappearance is also stylish sometimes in some cells suppose this is a nucleus right it gradually Fades away it gradually Fades away and then disappear this process where in the crotic cell nucleus become less and less basophilic because normally nucleus take which color basophilia gradually it becomes less and less basophilic and then it fades away it fades away nucleus Fades away this is called karyolysis what is it called area lysis so what is keriolysis this this appearance of necrotic cell nuclei by gradual digestion of its components and gradually fading away dasophilic Mass in some other situations nuclear cells nuclear sorry nuclear components they condense before they totally disappear they condense for example this was normal nucleus and with the time they become more condensed and then they become super condensed right and if they become very much condensed extremely basophilic Clump and shrunkan if in this fashion nucleus is disappearing we call it pecanosis we call it recognosis big noses right if this was keralises and this is and third style in which nucleus may disappear that is nucleus simply undergoes first of all condensation and then it undergoes fragmentation this intervals fragmentation and then disappear it is not nuclear blast by the way right so this is called Kaleo rexis Cario Rexes this is Kario rexes so again I will repeat as there are changes into cytoplasm which can be manifested by electron as light microscopy or by electron microscopy and there are changes in nuclei right nuclear cytoplasmic changes under the light microscope increase xenophilia glassiness and myelin figures are left which may be either totally Focus I Toes or if they stay longer they will become calcified electron microscopic changes yes plasma membrane disrupt disrupted or ruptured mitochondria are swollen with amorphous then stress and intracellular myelin figures and with amorphous fluffy denatured protein right how the nuclei undergo morphological changes the morphological changes in the nuclei of necrotic Cellars either they gradually fade away that is condense and clumped mass of basophilic material that is picnosis or the slightly condensed and then fragment that is called curio right now we will go to the different types of necrosis right uh first few words about coagulated necrosis what is coagulative necrosis coagulative necrosis is a type of necrosis in which a group of cells when they are lethally injured they are structural and functional proteins undergo denaturation simultaneously how classical example of this is again myocardial infarction right that let's suppose this is a piece of left ventricle right and there is a blood vessel here and which closes right there's a plaque and with that affirmative plaque with rhombus now the cells which are over here they will undergo coagulative necrosis now what is coagulative necrosis the special hormone Hull Mark of coagulative necrosis is that necrotic cells maintain their basic architecture and outlines at least for few days after the lethal injury has been done to these cells during the process of necrosis the necrotic cell maintain their cell ular architecture and cells outlines at least for few days why it happens so the reason is as I told you that in necrosis there is there are three components which occur number one I told you that there is denaturation denaturation of proteins right number two I told you that there is enzymatic digestion and and number three I told you that there is rounding inflammatory reaction inflammatory reaction now let me explain what happens in coagulative necrosis as I told you in the beginning that there are two types of categories of proteins they are structural proteins and there are functional proteins and outer functional proteins there are enzymes as well right now you imagine that if there is sphere ischemia or hypoxia here right and denaturation of protein starts if structural proteins and enzymes both undergo denaturation simultaneously listen as soon as it was very severe hypoxia to self right what will happen that in the cells very rapidly ATP levels will go down right and lactic acid levels will go up and protein will start undergoing denaturation if denaturation process is so severe and so broad spectrum that not only structural proteins undergo denaturation but simultaneously enzymes also undergo denaturation if enzymes are denatured it means they are non-functional and if they are not functioning can enzymatic digestion start there no a very big no no so what will happen cells will be frozen apparently cells will be Frozen that now look here this cell is a group of cells and these group of cells will be undergoing changes but enzymatic digestion or proteolysis is arrested proteolysis is arrested as the enzymes are denatured all digestion is delayed until the leukocyte come and they bring their enzymes so it means there is no auto license their own lysosomal enzions or their paroxysomes or other degradation systems they are frozen themselves then what will happen that as digestive process enzymatic digestion is delayed at least for few initial days cells structures will be well maintained right and gradually cells will become highly a synophilic and as you know as I mentioned in previous lecture that nuclei will disappear so very soon these necrotic cells will appear as if they are highly synophilic a nucleated cells highly xenophilic cells without nuclei is that right but opposite to that if we make a concept that structural structural proteins undergo denaturation but functional protein remain active enzymes remain active and even enzymes are very intensely active they will need to liquefaction of this tissue they will digest away the tissue but in coagulative process there is no digestion at least initially is that right is it clear so classical example of coagulative necrosis is myocardial infarction or any severe ischemic injury or hypoxic injury to most other tissues of the body severe hypoxia or ischemia to part of a liver or part of a kidney or part of a spleen right it may undergo coagulative necrosis right what is the Hallmark of coagulating necrosis again it is such kind of necrosis in which not only structural proteins undergo denaturation but enzymes also undergo denaturation almost simultaneously right so self structure is denatured and enzymatic processes digestion is not started right due to that reason as there's no auto license cells become deeply synophilic and over one or two days nuclei disappear but still cells maintain their structural architecture or self maintain their outlines is that right but as time passes by eventually when cell membranes are ruptured what happens inflammatory reactions start around this focus of necrosis and that inflammatory reaction will bring what what are these cells neutral cells So eventually inflammatory reactions start around these cells and neutrophils appear there right and they start digesting these cells but this digestion by neutrophil lysosomal this is not artolysis this is heterolysis and of course as time will pass by the second line of white blood cells will arrive there and that is what what are these macrophages and then macrophages will also come over here so neutrophil and macrophages will make inflammatory Zone around these coagulated necrotic material right and before it could really get completely digested before it could become completely digested and removed by neutrophils and macrophages local fibrocytes are converted into fibro blast and they migrate into this area these fibroblasts and they lay down what collagen right and gradually these cells are eaten up by neutrophils and macrophages and then as they disappear write this fibroblasts have deposited their collagen and Scar is formed over there so this is what happens during coagulative necrosis this is what happens during coagulative necrosis that before the tissue undergo extensive before the tissue undergo extensive digestion actually cells have been removed and leukocytes and fibroblasts start to initiate the repair process am I clear any question up to this right so this was about again very severe ischemia or hypoxia to most tissues of the body produces coagulative necrosis but there is one exception that is your brain your central nervous system if there is brain infarction cerebral infarction a brain stem infection unexpectedly that does not undergo coagulative necrosis that undergoes need to be effective necrosis it means if there is severe ischemia to part of the brain right dependent if this vessel is blocked dependent cells will undergo liquefaction what I mean by that these infected cells will undergo cerebral infarction cells will undergo leak reflection mean they will convert into a creamy viscous material what I mean that cellular outlines will not be maintained why it happens no one is sure why it happens but there are different speculations few authorities believe it is because in the brain and Central of a system structural architecture is not so strong structural proteins are not in massive amount other authorities say that in lysosomal enzymes are slightly different in central our system and they are more abundant so they cannot be completely Frozen and they digest away the tissue still other authorities believe believe that if effective necrosis may be because in central nervous system of course lipids are more right so all these things are put forward but one thing is very important that severe ischemia or hypoxia to almost all tissues of of the body produces coagulative necrosis is that right a localized area of coagulative necrosis is called infarct localized area of coagulative necrosis is called infarct right the only exception is central nervous system where severe hypoxic injury or ischemic injury lead to liquid Factor necrosis we are not very sure why it happens why in central nervous system when structural proteins undergo denaturation why enzymes remain active and it gets gets liquefied some authorities believe that different speculations there are three different reasons are brought forward again but none of them is very authentic one is probably in central number system structure proteins are less than the other solid organs secondly in central our system lysosomal enzymes are slightly more intense thirdly in central our system uh phospholipids are more due to so many membranes of the neurons okay now let's compare coagulative necrosis with liquid factor in acrosis what happens in liquid effective necrosis liquefactant necrosis is a type of necrosis where even though structural proteins undergo denaturation but there is intense enzymatic digestion so very simple here structural proteins in coagulative necrosis structural proteins undergo denaturation as well as doesn't occur at least initially right but here Leaf effective necrosis is a situation in which when an area of an organ or tissue undergo sphere necrosis even though structural proteins are denatured but enzymatic digestion is intensely going on into that tissue and severe proteolysis occur and component of those cells convert into liquid material right what could be the example first of all we should remember this thing liquefactant necrosis is where structural proteins proteins May undergo denaturation but there is intense enzymatic digestion digestion and this enzymatic digestion may occur due to autolysis it may be due to heterolysis hetero license because the areas where there is leak effective necrosis usually there are lot of leukocyte there and leukocytes in very massive number releasing lot of lysosomal enzymes which are trying to digest everything around is that right lot of and with that so it means heterolysis may be due to enzymes right derived from leukocytes or in these areas there may be a pyogenic organism organism which produces pus right like E coli or staphylococcus or streptococcus and they themselves also produce dangerous digestive enzymes plus these phyogenic organisms not only themselves produce digestive enzymes these organisms also give strong signal to accumulate neutral of health and neutrophils produce also digestive enzymes so leukocytes plus there are enzymes which are derived from microbes right pyogenic microbes usually it's a focal bacterial infection or sometimes even fungal so leaky effective necrosis is classically seen uh in pyogenic inflammations right past forming inflammation pyogenic organism is that right like streptococcus staphylococcal E coli clepsellas salmon organism like this which produce passenger organs or tissues now why tissue undergo liquid filtration it is very clear intense enzymatic digestion and here it is important because digestive process is very fast at the focus of injury so we can say that in liquid effective necrosis liquefactant necrosis tissue dissolution is faster than the repair process tissue dissolution by the enzymatic processes faster than the surrounding repair process hair tissue dissolution is necrotic tissue dissolution is slower than the repair process am I clear yes right now classical classical example of liquefactant necrosis should be passed now what is pass everyone knows what is past but let me make a little concept that when we say in one part of our body in a tissue or in an organ or in a confined place in the body there is pulse formation what we really mean medically what really happens let's suppose this is a tissue okay I will give you an example of liver right and if some pyogenic organism come here I will bring this area out okay these are the microbes very dangerous microbes which are very toxic producing dangerous destructive enzymes into the tissue and producing sphere inflammation is that right now in the area when these dangerous enzyme microbes come or bacteria come of course they will bring their what they will damage the local Health let me make local cells red so local cells are also there is that right and these are the bacteria infiltrating this tissue and there are local cells I will call them parenchymal cells and when the bacteria are damaging the cells then damage cells injured cells and bacteria both of them attract the neutrophils if there's intense neutrophil infiltration if there is intense neutrophil infiltration why in source of inflammation usually neutrophils arrives earlier than the macrophages who will tell me why neutrophils arrive usually at the site of acute Reformation neutrophils arrive first and macrophages arrive later why multiple reasons not smaller size my friend multiple is the number one the chemotactic agent from The Source focus of injury the chemotactic agent which attract the neutrophils they are produced initially and chemotactic agent a chemical mediators which attract the macrophages there monocytes when they come out of the blood vessel they become macrophage they have produced later secondly of course neutrophila more abundant than the monocytes and neutrophils are more mobile than the monocyte it's just like Warzone in the war zone the army jeep will come first for tanks will come first tank are slow to come the army jeeps will come first so neutrophils are like Jeeps and body defense neutrophils are more abundant so Jeeps are more abundant they are more faster than the tanks macro pages the more abundant they are more fast and call is given first to them hemotactic agent a chemical mediator so if next time someone asks you why neutrophil usually arrive first at the scene of acute inflammation right and later on macrophages come you will say light Jeep you know Jeeps like Jeep neutrophils are more abundant in any army jeeps should be more than the tanks so Jeeps are oh sorry neutrophils are more abundant more mobile and call is given to them chemical signals are given to them earlier but once neutral will come here and start fighting and if the field the fight is really tough then they give signal to the tanks they give chemical signal to the monocyte macrophages so that is why macrophage come later the multiple reason macrophages slow to extra visit they come out of blood vessel that the focus of injuries slowly they are lesson number right and then they then they are called also later on so first wave of leukocyte which comes neutrophil second wave of leukocyte which comes matter of Ages where are macrophages I didn't show here okay I will show the tanks here these are the macrophages where it right these are macrophages and another thing initially well tissues inflamed it is rich in neutrophil if injury continues for longer time gradually this area become pour in neutrophil and abundant macrophages what are the reasons one mechanism I already explained the initial injury within few hours neutrophils should be more and macrophage should be less I told you basic mechanism that neutral will come faster they are abundant and they come and they are more mobile macrophage are late to come and slow to come but another reason as days go by the Syria become very rich in macrophages why because neutrophil life is very short once the neutral will come into the war zone they die within few hours macrophage can live for weeks so tanks are slow to come but once they come they are there when you don't feel the Blasted away during the fight with even let me tell you one more thing if even macrophages become very frustrated then give they give a call to the lymphocytes they call lymphocytes but anyway will not go into that detail what I tell you in the process of formation of past what really happened there is acute inflammation severe injury usually by for example pyogenic organisms right and these organisms produce severe damage to the local health is that right and there then injured cells and pyogenic organism they call neutrophils and very soon there's a very big aggregate of what is there highly and highly dangerous microbe and leukocyte and injured cells now all of these are producing dangerous enzymes leucoside efforts first very dangerous enzymes are proteolytic enzymes are produced by this micro number two when cells are ruptured their lysosome produce dangerous enzymes then neutrophil come they also produce destructive enzymes so this area become very rich and destructive enzymes due to that Rhythm so much enzymatic activity goes on here that tissue undergo liquifyction that injured cell necrotic cell cannot maintain their outline structural outlines even for short time is that right and we say of course there's an inflammatory reaction here blood vessels are dilated and micro circulation is leaky and protein-rich fluid is coming into this area now eventually all Syria becomes yellow creamy color and we call this pus but what is past exactly let me tell you in this area when this such a hot water is going big war is going on what will be there number one there will be local cells there will be local cells now these local cells or parent chemical cell some of them will be alive in the area of past some of them will be alive some of them will be dying and some of them will be already dead it means in the past for example in the liver path there should be hepatocyte is that right it passes in the brain there should be a live data dying neurons is that right depending on the tissue so wherever this pulse is being formed what is there alive dead and dying alive and dead and dying local cells the parent chemical cells plus of course microbes are also being attacked by the neutrophils so some microbes are happy and some of them are suffering so there will be alive yes dead and dying what microbes thirdly leukocyte when they are jumping into fight and leukocytes are fighting white blood cells especially neutrophils are fighting there some of them the neutrophils in that area will be alive some of them will be dead or some of them will be dying so it is just like a war zone passes an area of war zone and in that war zone what happened there are some cells which are alive some are injured dying and some are already dead bodies so what is pass let's make it further and because of intense inflammation there is increased blood flow in that area and increased permeability from the micro circulation protein Rich absolute date is coming out protein rich exudate is coming out so what we can say there that passes an area of liquid effective necrosis passes an area of liquid effective necrosis it consists of it consists of a live dead and dying local self alive dead and dying microbes alive debt and dying neutrophils all floating into protein rich inflammatory oxidate all present in protein rich inflammation that is pass so now onward someone asked you what is passes an area of lip effective necrosis and in the past what is their composition of pass it's a protein Rich acidate having lot of live dead and dying local cells alive dead and day micro a live date and time now another example of liquid refractive necrosis is abscess what is the abscess now it's easy to understand abscess is actually localized pus which is in any deep tissue when a pass becomes localized in one area let's suppose in the liver here is pass now if the pus is here right it is localized from all side then we say this is abscess so what is abscess a pocket of path or path which is localized in a deep tissue or organ on a confined space in the body for example in peritoneum there may be pocket of pus or in the pleura some area Pocket of pass right then we call it abscess if it is localized is that right now if you look at the abscess right what you really find actually let me tell you abscess here first of all in the center of the abscess there will be lot of dead neutrophils dead neutrophils and that microbes and dead local cells slap around it there will be active neutrophils because neutrophils are coming from the surrounding area so dead bodies are Center and around that fight is going on so we say the Earth says in this heart of the abscess in the core of central core of the abscess what is there dead neutrophil along with dead cells and microbes around it there are a zone of preserved neutrophils or fully activated around that there is area of dilated blood vessels due to inflammatory reaction is the right and of course uh around this area if absence remain for a long time here then there is a attempt attempt of the tissue to repair so local cell let's suppose these are hepatocytes hepatocytes are trying to multiply around it because whenever there's inflammation and injury growth factors are also produced for the repair is that right even fibroblasts are also active there and they are trying to make some fibro so what is happening actually that at the outer margin zone of the abscess local cells are trying to proliferate so that they can compensate for the dead cells Plus lot of fibrotic reaction is going on fibroblast so that they try to wall off the abscess localize this area and even if it remain for that long time it cannot heal usually we need to drain the abscess because for it is Walled off and then it remain a focus of infection there so what is abscess another example of liquefactant necrosis right but remember liquefactive necrosis can be without pyogenic organism classical example is central nervous system and we simply just give me our epoxy I can produce liquefactant necrosis right that was a unusual situation but abscess is well localized pass in a deep organ all tissue or in a confined space which has where there has been seeding of seeding of pyogenic organisms abscess consists of a central zone of that neutrophil along with that local self surrounded by a zone of Highly active neutrophil and around that the dilated blood vessel sphere inflammatory reaction like blood vessels and parent chemicals that repair effort parent camel cells and fibro blast laying down lot of collagen right any question up to this we'll discuss about remaining type of necrosis like fibranoid necrosis cases necrosis or yes gangrinos necrosis and other type of fibrosis we will fat necrosis we'll talk in the next lecture okay class business