Asthma | Pathophysiology | Retired

[Music] hi ninja nerds in this video we are going to talk about asthma so let's go ahead and get started all right so let's go ahead and get started on asthma so first off how would we define asthma let's just get a basic definition of it okay before we start going into all the pathology and the underlying etiology the first thing that you want to understand is it's just it's a chronic inflammatory condition and it's characterized by having the narrowing of the respiratory passageways which can cause difficulty breathing sometimes it can even be extremely fatal so that's a simple definition of asthma it's just basically a chronic inflammatory condition of the respiratory passageways particularly the mucosa that causes the narrowing of the respiratory passageways to the point where it can become difficult to breathe and sometimes can become fatal now what are some of these underlying causes well we don't really completely know what is the underlying etiology of asthma we know that there's some type of genetic predisposition possibly through it and it's related through a specific type of triad and what we call that triad is called the atopic triad so the atopic triad is there is certain individuals who are uh have some genetic predisposition okay where they have more of allergic or hyper responsiveness to specific types of allergens what are these three conditions of this atopic triad well one is going to be asthma the other condition is going to be atopic dermatitis atopic dermatitis is also called eczema we'll write out the particular name though atopic dermatitis and the last condition that is going to be a part of the atopic triad is going to be allergic rhinitis okay allergic rhinitis these three conditions are the genetic predisposition might have a family history they might have some underlying genes that make them more predisposed to responding in such a way to particular allergens that cause them to produce massive amounts of inflammatory mediators that produce this exacerbation or bronchospasm of the actual respiratory passageways so these are some of the big ones so this is more likely to be the genetic predisposition of asthma okay so again individuals with the atopic triad is a genetic dispute disposition so maybe they have allergic rhinitis maybe they have atopic dermatitis or eczema or asthma this is usually the underlying genetic predisposition associated with them so they have the hyper responsiveness the other thing is it could be related to something really interesting which we call the samters triad so the santers santers triad and the sanders triad is three different things that makes these individuals more susceptible one of the big ones for the samters triad again we know that this is association with asthma nasal polyps and here's the big one aspirin we're going to write that as asa aspirin sensitivity what do i mean by this and some individuals they might have kind of an allergic or hypersensitive reaction to aspirin what do i mean well you know aspirin if we we actually talk about the uh arachidonic acid pathway so you know you have arachidonic acid we're just going to put a a here arachidonic acid goes through two different pathways one is it can go through a pathway which is utilized by the cox enzyme so cyclooxygenase enzyme the other one is it might go through a lipo oxygenase pathway the lipo-oxygenase pathway leads to the formation of leukotrienes and there's many of these different types okay so if you wanted to know some of them there's leukotrine b4 there's leukotrine c4 leukotriene d4 leukotrine e4 there's so many of these and all of them have specific functions usually leukotriene b4 is a pretty good chemotactic agent and leukotriene c4 d4 and e4 these are the culprits behind that intense bronchospasms okay the other pathway is for the cyclooxygenase pathway this leads to the formation of prostate and there's many of these there's pg e2 pg i2 pg f2 there's many of these all of them have again multiple different functions but here's the thing in some individuals they have this situation where they have a sensitivity to aspirin where aspirin you know what it does right it actually inhibits the cyclooxygenase enzymes which are responsible for converting arachidonic acid into prostaglandins for some reason whenever these individuals take aspirin it inhibits this pathway in such a way that it actually can start tipping the balance and shunting the arachidonic acid into the leukotriene pathway why is that important what did i tell you was leukotriene c4 d4 and e4 responsible for bronchospasm increased vascular permeability and it also can cause a lot of mucus production within the airways those are the big morphologies that we're going to see when we talk about asthma particularly when we get down into the bronchi or the bronchials okay so those are the big things here so again asthma it's a chronic inflammatory condition characterized by narrowing of the air passageways what could be the causes it could be underlying genetic cause so it might have a genetic predisposition especially in individuals who have atopic dermatitis or eczema allergic rhinitis or asthma could be related to some other underlying mechanism specifically to aspirin sensitivity and also make sure that you look in because sometimes patients who have aspirin sensitivity might have nasal polyps or asthma and the reason why this is important is because with aspirin sensitivity it can tip the balance by inhibiting the cox 2 or cox 1 enzyme which aren't able to make prostaglandins and then it shifts it into forming leukotrienes and the big big ones that you got to remember is c4 d4 and e4 because these are the ones that produce intense bronchospasms okay but there's many other situations that could exacerbate asthma or cause it to you know come about what are some of these triggers well one of the big ones is usually like certain types of dust so one could be dust so dust mites could be pet dander so it could be pet dander or pet hair it could be due to bugs you know cockroaches cockroaches are actually been found to be able to be an exacerbating factor it could be due to cold and it could even be due to exercise so sometimes exercise can even be related to it here's another really really big one though i want you to remember usually viral upper respiratory tract infections this is a big one sometimes whenever when somebody actually develops a viral uri it can actually trigger an exacerbation of asthma that's a big one and sometimes even emotional stress another one that i want to mention is smoke right so not just dust but even don't forget smoke inhalation so for like tobacco right tobacco smoke or certain types of air pollutants another medication that has actually been found to do this to trigger the asthma is not just aspirin but sometimes even people who are taking beta blockers why because you know beta blockers actually respond by binding to beta receptors well guess what kind of beta receptors are present on the smooth muscle within the actual bronchials beta 2. so if somebody has a beta blocker the epinephrine or the norepinephrine which is normally binding onto the beta2 receptors and promoting bronchodilation is going to be blocked and what's that going to do it's now going to lead to bronchoconstriction so that can cause an exacerbation of asthma as well so to recap all of these exacerbations and triggers it could be atopic genetic could be due to medications like aspirin sensitivity related to the sampler's triad or beta blockers it could be related to certain types of chemicals like dust pet dander and hair cockroaches cold temperatures exercise viral upper respiratory tract infections like the common cold and smoke inhalation whether it be through tobacco or certain types of pollutants now these are some of the things that we know are responsible and as well as triggering asthma what we need to do is is we need to go into this a little bit more and talk about the molecular mechanism because we've kind of come to an understanding of how the molecular mechanism works so what we say is again let's say that there's some type of predisposition okay and what happens is let's say that there's a particular allergen okay so here we're going to have here this is going to be the allergen maybe it's dust maybe it's mold maybe it's something of that nature this allergen is going to come into contact with specific types of antigen presenting cells what are those antigen presenting cells one of the big ones that you guys should know about is called your dendritic cells but even macrophages so here look at this guy we draw the dendritic cells because they have multiple different cytoplasmic extensions but here's a dendritic cell what a dendritic cell will do is it'll phagocytose these allergy like particles when it phagocytoses it so here let's write that down there it undergoes phagocytosis and it also is going to activate particular genes you know chromosome number six there's the mhc2 molecules it'll actually take phagocytosis break it down via the phagolysosome mechanism activate the mhc2 complexes and express that allergen with an mhc2 complex on its cell membrane so now look at this we're going to have an mhc2 complex let's do this in purple so here he's going to have a mhc2 complex here here's our mhc2 complex and again what's expressed on that is we're going to have that actual nice little allergen so here we're going to have the allergen that dendritic cell then takes this actual mhc2 complex with the particular allergen and brings it to a t helper 2 cell so let's draw a nice little t helper 2 cell in here let's do this guy in this dark green here so here we're going to have a t helper 2 cell look at this guy what does a t helper 2 cell express on its cell membrane specific to this one of the big things is it has a cd4 molecule and another thing that it has on its membrane is a t cell receptor which is particular to a specific foreign antigen now this t helper 2 cell will react with this dendritic cell so let's bring this dendritic cell down here to react with this guy here's our dendritic cell and again what do we have here we're going to have the mhc2 molecule and on this mhc2 molecule we're also going to be presenting what we're going to be presenting that for an antigen which is this allergen which is going to bind with the t cell receptor whereas the cd4 molecule is going to interact with the mhc2 molecule now upon this interaction the t helper 2 cells undergo a inappropriate type of reaction in a way because again this underlying condition underlying genetics or even environmental relationships and what it does is it produces two really important chemicals what are these two chemicals one is called interleukin four and the other one is called interleukin five interleukin-4 is really important what interleukin-4 does is it actually activates our plasma cells so let's do here we're going to have it's going to activate the plasma cells so this is going to be our plasma cells with a nice rough endoplasmic reticulum so the interleukin 4 is going to be released here let's actually do this like this we'll have interleukin 4 being released and that's going to act on these plasma cells when it acts on the plasma cells it's going to stimulate the plasma cells to produce specific types of antibodies you know what specific antibodies it actually produces i g e antibodies and it produces a lot of them these ige antibodies then go and bind onto particular cells and guess what these cells are these cells are called mast cells so now we're going to have here mast cells the mast cells have a specific protein on their membrane called an fc epsilon r1 receptor fc epsilon r1 receptor which binds with the ige antibodies then once this ige antibody binds here it then can trigger the mast cell to undergo degranulation when it degranulates it starts to produce massive amounts of histamines and it produces a lot of leukotrienes again there's many of them we've already talked about them but these are we know are inflammatory mediators that's the first response the other chemical that we mentioned here is going to be interleukin 5. so interleukin 5 guess what this guy does interleukin 5 goes and activates a particular white blood cell that we know has two really important functions one is we know it's related to killing parasitic worms the other one is we know it plays a complex role in allergy and asthma well guess what that guy is it's an eosinophil so now here we're going to draw a red structure here it has a bilobe nucleus which kind of looks like glasses look at that look he's chilling here we'll put the glasses there all right and then you're going to have the granules which stain red because of the eosin that they apply via the right stain now the interleukin 5 is going to activate this eosinophil so again what is this guy here this is a eosinophil this eosinophil is then going to release leukotrienes and it's also going to release other cytokines which are going to attract in more white blood cells but you know what else it can do which is very important it can also release specific types of proteases and these proteases over time chronically can start to produce tissue damage to the respiratory tract so this is really important especially in chronic cases but what i want you to remember for right now in the acute response is leukotrienes and other cytokines that help too attract in more white blood cells particularly more eosinophils now from here these histamines and these leukotrienes what do you think these puppies are going to go do they're going to go affect the actual bronchioles so now look here we have these histamines we have these leukotrienes from both the mast cells and from the eosinophils going where affecting the bronchioles okay all of this is actually happening in the actual submucosa the mucosa area of the bronchioles now again over here what do we say from the aspirin sensitivity excuse me via the sampler's triad we know that the leukotriene c4 d4 e4 is pushed to making more of those especially people who have aspirin sensitivity so again from this one you're going to have a lot of leukotrienes coming here and acting on these actual bronchials isn't that beautiful isn't on it it should make sense now because we know that leukotrienes and histamines what are they going to do well if you remember histamines i want you to remember the big thing with histamines one thing is it normally purdue produces smooth muscle relaxation right but in this case for the respiratory smooth muscle it actually causes constriction so one of the big things is going to happen here is it's going to cause bronchoconstriction so let's write this down here let's do this one and this brown so we know the first thing that's going to happen is there's going to be broncho constriction now this is a really big one bronchoconstriction is whenever the smooth muscle is going to contract they're going to be hyper reactive they might even over time become hypertrophy and even hyperplastic which means you can make more of them or the cells get bigger right so hyperplasia you make more of them hyper hypertrophy they actually get bigger that would be over chronic periods of time but bronchoconstriction is going to narrow that airway pretty bad the next thing is histamines also cause dilation of the capillaries and cause increased capillary permeability so what else are you going to get here you're also going to get a lot of increased vascular permeability and a lot of inflammation guess what that actually helps to stimulate a lot of mucus production so then on top of the bronchoconstriction you're going to get a lot of mucus buildup here because it's going to increase the vascular permeability as well as try to dilate the actual capillaries in this area so you're going to get mucus build up so that's another big one so bronchoconstriction and mucous buildup what else another thing is we also said that this mucosa is gonna become super inflamed it's gonna fill with a lot of fluid so that's another thing is you're gonna notice that this actual mucosa here which you're going to have your epithelial tissue is the first part of the mucosa then you have your lamina propria well you're going to have to start filling this with a lot of fluid so now the mucosa is going to become filled with fluid and some eosinophils and other different types of inflammatory exudate so you're going to have a inflamed right mucosa and again we said the leukotrienes that i want you to remember with these guys is they help to be able to promote bronchospasm they also cause mucous buildup they also cause the inflammation of the mucosa but again one more thing that we can't forget is there's going to be an increase in vascular permeability okay so these are the things that we're going to see so there's going to be constriction there's going to be mucous buildup which is also going to be narrowing the airways there's going to be inflammatory exudate due to the increased vascular permeability and immune cell infiltration that's also going to narrow the airway so all of that should make sense why the airway is actually narrow now this is usually an acute response right but over time over chronic consistent exposure and this chronic exacerbations it can become fibrotic so over time now generally here's what you want i want to write this down actually very very important asthma is reversible so in other words you take away the trigger or you treat them with the appropriate medication it can be reversed they can go right back to normal and the respiratory passageway can actually not cause this intense bronchoconstriction the mucus buildup will go away the mucosa will no longer become super inflamed the vascular permeability will go back to normal right but again i want you to understand over chronic terms of this consistent exacerbations of asthma it can become fibrotic it can scar there can be thickening of the basement membrane and become permanently narrow that is no bueno we don't want that okay so that's an important thing to understand one last thing i want to mention before we end the pathology and move into the signs and symptoms is there was one more thing that they've related asthma to be due to and again it's controversial but they relate it environmentally to what's called the hygiene hypothesis and again they're still kind of like working this whole theory out hygiene hypothesis this is specific for late onset asthma usually because asthma is mainly having a genetic aspect via the atopic or via the sampler's triad this hypersensitivity that usually helps us to diagnose it before the age of 12. but with environmental it's usually a little bit later now what does this mean hygiene hypothesis says that people who have had reduced exposure to bacteria or viruses or pathogens they are more likely or more susceptible to develop asthma later on in life because of some type of effect on actually the maturation of our actual white blood cells okay so that's one theory that they've gone through but again this is more for the later onset of asthma all right so that's the the pathophysiology of this the next thing we're going to do is we're going to go over the signs and symptoms all right so in this video we talked about the pathophysiology of asthma i know we talked about a lot of stuff i hope it made sense i hope you guys enjoyed it if you guys did please hit that like button comment down in the comment section and please subscribe in the next video we're going to go over a lot of the actual diagnostic work up a lot of that protocol being able to figure out is this asthma or is this something else okay if you guys like this video again hit that like button comment down in the comment section and please subscribe also if you guys get a 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Channel: Ninja Nerd

Views: 460,630

Keywords: Ninja Nerd Lectures, Ninja Nerd, Ninja Nerd Science, education, whiteboard lectures, medicine, science, Asthma, pathophysiology of asthma, pathophysiology, symptoms of asthma, exercise induced asthma, asthma series, asthma pathophysiology, pulmonary medicine

Id: uQL7AYyBR-Q

Length: 23min 7sec (1387 seconds)

Published: Tue Jan 05 2021