Acute Inflammation Made Easy

hi I'm Dr Omar Malik and in this video we'll talk about acute inflammation so let's first start by understanding the basic concepts of acute inflammation suppose you get a cut on your skin what do you think happens at the molecular level in that cut of course some cells will be damaged there and microbes like bacteria will be able to get in a reaction to this the tissue and the blood vessels in that area develop a response that allows your body to contain the problem and get rid of the bacteria how exactly your body does this will be discussed later in the video so what exactly is inflammation in simple terms it's the body's response to harmful agents such as pathogens or damaged cells the aim of this response is to bring white blood cells and defense molecules from the bloodstream to the affected area to eliminate the thread and begin the healing process before we proceed further it's very important for you to understand the pattern of questions that have been asked from this topic in the last 10 years and how that pattern of questions has changed over time during the 2012 to 2015 exams the questions from this topic focused more on the basic concepts distinguishing between acute and chronic inflammation and cardinal signs of inflammation then during 2016 to 2019 the type of questions shifted towards a deeper understanding of cellular mechanisms mediator of inflammation and morphological patterns of inflammation but during the last 3 to 4 years that is from 2020 to 2024 the questions have become more integrative requiring knowledge of clinical applications molecular mechanisms and Recent research topics hence it's very important for you to focus on the latest trend of questions so let's continue with our

topic and try to understand the basics of inflammation is basically of two types acute and chronic here are some important differences between the two acute inflammation develops rapidly within minutes 2 hours whereas chronic inflammation develops slowly within a few days the cellular infiltrate in acute inflammation is mostly neutrophils whereas in chronic inflammation monocytes macras and lymphocytes are the predominant cell type acute inflammation causes less tissue damage which is usually self-limiting but in chronic inflammation the tissue injury can be severe and can even progress with time acute inflammation involes some prominent signs like pain redness raise temperature Etc but chronic inflammation has less prominent signs acute

inflammation basically consists of two main types of responses the first involves the response of the blood vessels and the second response is of the cells let's break down and try to understand and what actually happens in both these cases first we will talk about the changes that occur in the blood vessels let's continue with our previous example of a cut on a skin the blood vessels first undergo Vaso constriction but then they quickly relax and undergo vasod dilation the initial vasoconstriction in acute inflammation is a brief reflex response aimed at minimizing blood loss and facilitating clot formation at the site of injury It prepares the blood vessels for subsequent Vaso dilation which increases blood flow and brings immune cells to the area this phase is mediated by neurogenic reflexes and substances like endothelin and camines like we just discussed after this the blood vessels quickly switch to vasodilation which is the main response of the blood vessels in acute inflammation this widening is what causes that redness and warmth you often see in an inflamed area because now due to vasor dation more blood is being delivered to that area in acute inflammation increased vascular permeability is essential so that immune cells and defense molecules can exit the blood vessels and reach the site of injury or infection several mechanisms contribute to this increased vascular permeability the most common cause of vascular leakage is the contraction of endothelium cells creating gaps that allow fluid to escape this is triggered by mediators like histamine and brinin and is known as the immediate transient response typically lasting for 15 to 30 minutes in some cases such as with sunburn or mild injuries a delayed response can also occur where vascular leakage begins hours later and lasts longer the second mechanism which contributes to increase vascular permeability is endothelial injury now direct damage to endothelial cells which are the cells lining the inner wall of the blood vessels can occur due to severe physical injury or microbial toxins this leads to cell necrosis and Detachment resulting in sustained leakage neutrophils adhering to the endothelium during inflammation can exacerbate this damage prolonging the leakage until the vessels are either thrombosed or repaired often mult mulle mechanisms contribute to increased permeability in blood vessels such as in thermal Burns where both endothelial contraction and endothelial injury play a role this can result in significant fluid loss which can be lifethreatening in severe burns the lymphatic system also responds to inflammation by increasing lymph flow to drain the excess fluid lucos sites and debris from the inflamed area this can lead to secondary inflammation of lymphatic vessels known as lymphangitis or lymph nodes known as lymph adenitis often marked by enlarged painful lymph nodes red streaks near a skin wound can indicate lymphangitis often signaling a bacterial infection now that we' have got the blood vessels sorted let's talk about what the white blood cells are up to during this time the First Responders here are neutrophils think of them as the body's emergency they start by moving from the middle of the blood vessels to the edges or the margins of the blood vessels hence known as margination then they start rolling along the vessel walls kind of like they are checking out where they can find an exit this rolling action is controlled by special molecules called selectins which are proteins attached to the neutrophils and endothelium of the blood vessels eventually these cells stick firmly to the vessel wall thanks to special proteins known as integrants once they are stuck the neutrophils can then squeeze through the gaps in the vessel ball and this is called transmigration or diabetes and then they head straight to the site of inflammation to take care of the problem now let's talk about lucite

adhesion molecules in a bit more detail these are special proteins that are present on endothelium and lucites and they lead to ad and transmigration of lucites here you have to remember about three main types of adhesion molecules first we have selectin two main types of selectins are involved known as p selectin and E select selectin play a critical role in the initial weak adhesion of lucites enabling them to slow down and Roll Along The Vessel wall on the white blood cells we have attachment proteins known as integrin lead to a more stable addision of lucites to the endothelium integrin attached to intracellular adhesion molecule or IAM one a key protein on endothelial cells facilitating firm adhesion different types of indig are present on different types of wbcs like lfa1 or lymphocytic one which is present on neutrophils then we have mac 1 on monocytes and vf4 on te- cells and monocytes we also have peam 1 also known as cd31 it plays a significant role in the process of transmigration where lucites move between endothelial cells to enter the tissues remember cyto keines like tnf Alpha and il1 increase lucite adasion molecules all this has been discussed in much more detail in our beautifully Illustrated handcraft CED medsimplified notes they cover every detail from this topic that you need to master and remember this topic for exams plus our McQ modules will help you to test your knowledge and prepare for exams confidently so if you are interested you can check the notes in the links provided in the description box down below genetic deficiencies of lucite adion molecules lead to increased susceptibility to bacterial infections there are two import important genetic defects associated with lucite adhesion molecules which lead to a deficient immune system these are lucite adhesion deficiency type 1 and 2 defects in integrant lead to lucite adasion deficiency type 1 or led1 is characterized by recurrent bacterial infections delayed wound healing and absence of P formation one of the first signs of LED type 1 is a delay in the Detachment of Amal cord stump after birth now genetic defects in selectins are seen in Lucy adhesion deficiency type 2 it also results in recurrent infections but with additional features like growth delay and Bombay blood group the child also suffers from severe intellectual defects a number of questions have been included from this section in latest exams let's review a couple of them question one a 2-year-old child presents with a history of recurrent bacterial infections and delayed separation of the umblical cord laboratory trests reveal is of course lucite adhesion deficiency type one question number two a deficiency in which of the following leads to the inability of Lucy to transmigrate Across the endothelium here are the options the answer to this question is peam 1 so now we have understood about the basics of acute inflammation let's try to understand what happens after this continuing the

example of a cut on the skin suppose some bacteria get in through the sight of injury so it's important that your white blood cells spring into action fast imagine they're like a battalion of soldiers and they have to fight the enemy which has crossed into their territory the enemy was spotted by the guard towers and the guard towers send a message over the wireless that they need help with this example let's try to understand what happens in your body when a similar situation arises After exiting the bloodstream dream lucaites move toward the side of injury by a process known as chemotaxis chemoattractants are those substances that lead to chemot taxis for example the peptides and lipids present in bacterial cell wall act as chemoattractants you can compare chemo attractants to the message that was sent by the guard towers to the Battalion of soldiers who after receiving the message know the exact location of the enemy and the movement of these soldiers is the chemotaxis for the purpose of exams you have to remember some important chemo attractants which are own body produces cyto interlukin 8 is a classic example it guides neutrophils to the site of injury then we have complement system components like c5a which is a powerful chemoattractant then we have arachidonic acid metabolites such as Lucine B4 or ltb4 which is also a powerful chemo attractant we'll study about the compliment system and the arachadonic acid metabolites in our next video where we will discuss the different mediators of inflammation these agents bind to specific receptor on lucites activating them to move towards the site of inflammation the lucites move by reorganizing their internal structure much like how a car with front-wheel drive is pulled forward by its Wheels persistent neutrophilic

infiltrate can be seen in infections like pseudomonas where neutrophils continue to be recruited for several days in viral infections we typically see an influx of lymphocytes rather than neutrophils and in allergic reactions and helminthic infections eosinophils are the dominant cells now we have a brief understanding of acute inflammation let's understand how our cells recognize harmful microbes and damage cells which is essentially the first step in phagocytosis which we'll discuss after this our cells have specialized receptors like tolllike receptors that act as early Warning Systems these receptors are found on different parts of the cell including the plasma membrane endosomes and cytosol allowing them to detect invaders no matter where they are our cells also have nlike receptors or nlrs that detect internal danger signals like uric acid and ATP which come from our own damaged cells these receptors activate a protein in the cell known as inflammosome which then induces the production of interlukin one a key molecule that recruits white blood cells to the site of damage in addition to the primary receptors that directly recognize microbes many lucites possess other specialized receptors one of the key types of these receptors are those that bind to the FC Tales of antibodies and complement proteins now what does that mean when a microb invades the body the immune system often tags it with antibodies or complement proteins this tagging process known as opsonization makes it easier for immune cells to identify bind to and ultimately destroy these Invaders these receptors on Lucy recognize these tag promoting the ingestion and destruction of the microbes lastly circulating proteins like those in the compliment system and Manos binding lectin play a crucial role in recognizing and attacking microbes

further fueling the inflammatory response now that we have explored how lucites are recruited to the site of infection or injury let's dive into the next crucial step how these cells recognize engulf and then destroy these harmful agents through the process of Phagocytosis is the method by which neutrophils and macrofagos the body's primary fyes engulf and Destroy microbes and dead cells here's how it works the first step is recognizing the enemy fyes have specialized receptors that help them identify and attach to harmful agents and cells we have discussed some important receptors which help wbcs to detect pathogens earlier in this video in addition to them Manos receptors present on mcroof fages is also one such example with this the macras is Bine to sugars like Manos and fucose which are found on the microbial surfaces but not on human cells allowing the fosite to distinguish between self and foreign cells we also have something known as opsonins like IGG antibodies and c3b component of the compliment system we'll discuss more about these in a bit and fyes have high Affinity receptors for these opsonins facilitating the process of recognition of pathogens which are qued with these opsonins the second step in phagocytosis is engulfment once the fosite has attached to its Target it engulfs it by extending its cytoplasm around the particle forming a fome which is basically a membrane bound iicle inside the cell the phagosome then fuses with a lome creating a fome where the actual Dees of the particle takes

place and the third step is intracellular killing and degradation inside the fome the fosite unleashes a barrage of toxic substances to kill and break down the engulfed pathogen you can imagine them as the weapons and bullets of the soldiers in neutrophils these enzy enzymes and chemicals are stored inside special structures known as granules which are of two types specific or secondary granules and azurophilic or primary granules each type of granule contains a distinct set of enzymes and proteins that serve different functions in the immune system let's first talk about specific or secondary granules these smaller granules are packed with enzymes that help in breaking down various extracellular components they include lysozyme which breaks down bacterial cell walls collagenases degrade collagen and gelatinase breaks down gelatine and other Matrix proteins we also have lactoferrin which binds to iron and deprives bacteria of this essential nutrient then we have histaminase and alkaline phosphatase which are important enzymes present in secondary or specific granules next we have the azurophilic or the primary granules these larger granules contain more potent antimicrobial substances like myop peroxidase which is a key enzyme and plays a critical role in generating hypochloride which is a potent bacteriocidal agent means it kills bacteria aurophilic granules also contain a variety of bactericidal proteins like defensins which disrupt bacterial cell membranes and acid hydrolases which break down various biomolecules within the fome additionally neutral proteases such as elastase cathepsin G and non-specific collagenases degrade extracellular Matrix components contributing to tissue Remodeling and sometimes tissue damage out of these it's very important for you to understand the functioning of acid

and neutral proteases acid proteases are enzymes that operate within the acidic environment of the phagosome where they degrade bacteria and cellular debris they are crucial for the digestion of engulfed pathogens neutral proteases on the other hand act outside the fome and can degrade various extracellular Matrix components such as collagen elastin and cartilage while this activity is important for tissue remodeling it can also lead to tissue destruction during chronic inflammation neutral proteases also play a role in activating other components of the immune system such as complement proteins and kinin by breaking down their precursor molecules the release of lysosomal enzymes into the extracellular space can cause significant tissue damage especially if not properly regulated this can lead to the amplification of inflammation and contribute to Chronic inflammatory conditions the body controls the activity of these powerful enzymes through antiproteases found in serum and tissue fluids the most important of these is Alpha 1 antirion which inhibits neutrophil elastis deficiency in alpha 1 antipin can lead to unchecked elastase activity resulting in conditions like osma due to destruction of elastic fibers in the lungs deficiencies in losal enzymes can lead to buildup of undigested pathogens or substrates within the cells contributing to a variety of losal storage disorders these will be discussed in much more detail in our biochemistry video series I'll provide the links to all the related videos in the description below now let's talk about some topics that have been recently added in the textbooks of pathology cellular interactions and behaviors within tissues are complex and varied two phenomena that illustrate these interactions are empiric pois and

entosis while they may seem familiar at first glance both involve one cell being engulfed by another their mechanisms outcomes and clinical implications are completely different emperipolesis is a process where one cell is engulfed by another without being destroyed unlike phagocytosis where the engulfed cell is digested and typically dies in emperipolesis The engulfed cell remains intact and viable within the engulfing cell this non-destructive interaction means that the engulfed cell can continue to function normally while residing within the other cell the precise mechanism of emperipolesis is not fully understood but it is thought to involve interactions between surface molecules of the engulfing and engulfed cell allowing for a non-destructive engulfment process emperipolesis is a area of active research particularly in understanding its role in disease processes and its potential implications in cell therapy and transplantation in autoimmune hepatitis emperipolesis is often observed in the liver where lymphocytes which are the engulfed cells are found within the hepatocytes which are the engulfing cells this phenomena is considered a Hallmark of the disease and can play a role in the immune response observed in this condition rosai Doan disease is a rare disorder characterized by Massive lymp adenopathy in this condition emperipolesis occurs when histiocytes which is a type of immune cell engulfes lymphocytes this phenomena is one of the key diagnostic features of this disease in Milo dysplastic syndrome which is a group of disorder caused by poorly formed or dysfunctional blood cells emperipolesis can be seen in the bone marrow the engulfment of hematopoetic stem cells by Mega caros sites is noted although the exact significance of this in MDS is still under investigation entosis is a unique cell within a cell phenomena where one cell actively invades another leading to the engulfment of the weaker cell by a dominant one unlike emperipolesis osis results in the death of the engulfed cell which is ultimately digested by the engulfing cell osis is closely associated with the adasion molecule ecin in Normal issues ecin helps to maintain cellto cell Adis however in tumors where ecin expression is often lost or reduced cells lose their cohesion allowing one cell to invade and engulf another once inside the engulfed cell is encased in a vacuum and eventually degraded by the engulfing cells lomes this process can be viewed as a form of cannibalism where the dominant cell consumes the weaker one often to gain energy or nutrients entosis is most commonly observed in cancerous tissues where it may contribute to tumor progression and survival in aggressive tumors cells exhibiting osis May gain a survival Advantage by consuming neighboring cells to meet their energy requirements this phenomena can also contribute to tumor heterogenicity making the cancer more resistant to treatments given its association with aggressive tumors osis is being studied as a potential marker for poor prognosis in certain cancers it also raises interesting questions about the role of cell competition and survival within tumors entosis is a relatively newly recognized phenomena and is a subject of ongoing research scientists are investigating its potential role in cancer metastasis resistance to chemotherapy and as a target for Noble cancer therapies while emperipolesis is generally non-destructive and seen in benign conditions or immune responses osis is destructive and is associated with malignancy this Stark difference highlights the diverse ways in which cells can interact with one

another in addition to their well-known roles in phagocytosis and microbial killing neutrophils have another powerful weapon against infections neutrophil extracellular traps Nets are webik structures composed of DNA and other nuclear materials that trap and neutralize pathogens at the site of infection let's break down how neutrophil extracellular traps are formed and why they are significant neutr extracellular traps are produced when neutrophils encounter infectious agents like bacteria and fungi or when they are stimulated by inflammatory signals such as chemokines cyto complement proteins and reactive oxygen species the process begins with the activation of an enzyme called Arginine damin which triggers chromatin decondensation other enzymes like Milo peroxidase and elastase then enter the nucleus and further loosen the chromatin structure this process eventually leads to the rupture of the nuclear envelope causing the chromatin to spill out into the extracellular space forming a sticky meshwork that traps microbes reactive oxygen species plays a crucial role in activating Arginine Damas leading to the conversion of arginine to Citrine and initiating chromatin decondensation then we have myop peroxidase and elastase and these enzymes further degrade the nuclear structure the formation of neutrophil extracellular traps result in the death of the neutrophil as its nuclear contents are expelled to form the Trap let's look at the function and importance of neutrophil extracellular traps once formed these traps act as a physical barrier concentrating antimicrobial substances like peptides and enzymes at the site of infection this helps to trap and kill the invading microbes preventing them from spreading to other areas of the body however the process isn't without its drawbacks Nets have been detected in the blood during conditions like sepsis where they can contribute to systemic inflammation Additionally the release of nuclear material into the extracellular space can potentially trigger autoimmune responses in diseases like systemic lupus aratos the DNA and proteins in neutrophil extracellular traps might act as autoantigens leading to an immune reaction against the body own tissues acute inflammation presents with characteristic morphological

features most notably the dilation of small blood vessels and the accumulation of lucites and fluid in the tissues however depending upon the cause severity and location of the inflammation several distinct morphological patterns May emerge recognizing these patterns is crucial because they often provide valuable clues about the underlying cause of the inflammation serious inflammation is characterized by the exudation of a cell poor fluid into the spaces created by cell injury or into the body cavities such as Peroni plura or pericardium the fluid typically lacks microbes and large number of lecco sites making it less dense and less likely to cause bus formation this type of inflammation is often seen in conditions like Burns or viral infections where fluid accumulates under the skin as in blisters or in body cavities a condition known as effusion when there is a significant increase in vascular permeability larger molecules such as fibrinogen escape from the blood leading to the formation of fibrin deposits in the extracellular space fibrinous inflammation is commonly seen in the lining of the body cavities such as the meninges pericardium and plura if not cleared fibrin can lead to scarring by stimulating the growth of fibroblasts and blood vessels potentially resulting in the thickening of tissues and the obliteration of spaces such as the pericardial space poent inflammation is defined by the production of pus which is an exur consisting of neutrophils necrotic cell debris and fluid this type of inflammation is typically caused by pyogenic plus forming bacteria like stfy cocai which lead to tissue necrosis a common example is acute appendicitis absess which is a localized collection of P within tissues organs or confined spaces often form as a result of bacterial infection these abscesses have a central area of necrosis surrounded by preserved neutrophils with surrounding areas of vascular dilation and fibroblast activity indicating chronic inflammation and tissue repair an ulcer is a local defect or excavation of the surface of an organ or tissue produced by the shedding of necrotic tissues ulceration typically occurs in areas where tissue necrosis and inflammation exist close to a surface such as a mucosa of the mouth stomach intestines or the skin of the lower extremities peptic ulcers of the stomach or duodenum are classic examples where both acute and chronic inflammation coexist the acute food phase is marked by intense neutrophil infiltration and Vascular dilation while The Chronic phase involves fibroblast proliferation scarring and the accumulation of immune cells like lymphocytes and macrofagos so this was all about acute inflammation I hope you like the video I provided links to met simplified notes in the description box down below so make sure to check them out and yes make sure to hit the Subscribe button below because we are going to upload a lot of videos in the coming time thank you so much for watching