Transition of Gingival Health to Disease PDF

We're going to go over the histological and clinical features of health and disease. What is the pathway from gingivitis to periodontitis? Does gingivitis always lead to periodontitis? How does clinical attachment loss take place? The origin, development and progression of periodontal disease and th...

We're going to go over the histological and clinical features of health and disease. What is the pathway from gingivitis to periodontitis? Does gingivitis always lead to periodontitis? How does clinical attachment loss take place? The origin, development and progression of periodontal disease and the role of the host derived inflammatory mediators and mediators in the pathogenesis of periodontal disease. So I hope at the end of the lecture you kind of have a great understanding of all these topics. So kind of go over what gingival health and disease is. We really have to understand what health is. We have to see what is normal to understand what is abnormal. So according to Who, health is a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity in disease, we have a pathogenesis or the origin and development of a disease, which is a step by step process that leads to the development of a disease that results in a series of changes in the structure and function. And in our case, for paired ontology, it would be the periodontal. So like I said, we have to really understand what is gingival health before we could understand what is gingivitis, what is periodontitis. So we'll briefly go over, you know, the clinical features of gingival health, histological features of gingival health and how we identify gingival health. So firstly, and I know it might seem kind of redundant. Healthy gingiva is pink. It's firm. It's resilient. It follows the flow or the shaping of the of the teeth. It may be stippled and it may be pigmented. This photo is kind of a blown up version of stippling of the gingiva. A lot of times students come to me, they think it looks abnormal, but this is just normal. Some patients may have it, some patients may not. We also have. Um, pigmentation. And so we can get pigmentation from Genesis, the degree of epithelial characterization, the depth of epithelial ization and gingival vascular parity. These colors can be uniform, they can be bilateral or they can be very blotchy. It can involve the papilla alone, the entire gingiva or even regions of the mucosa. The pigmentation of a patient tends to be lighter in fair skinned patients and blonds, and darker and darker skinned patients and darker haired patients. And you can actually see up here this darker area that's pigmentation. And like I said, a lot of times students come to me, they say, you know, I see some discoloration of the gingiva. It doesn't really look normal to me, but this is just, you know, normal pigmentation. And like I said, sometimes you see it more in darker hair individuals versus like blonder hair individuals. We can also have a thick or thin phenotype. And one way to determine this is actually if you put the probe through while you're probing, you can actually see the probe through the gingiva. That's a good way to tell if we have a thin or a thick phenotype. We could also have a thick scalloped type, thick and flat, as well as a thin and scalloped. So now you kind of have an idea of the different types of tissue that we can see in clinical gingival health. So next we kind of look at what are some other features we have. Like how much width of keratitis gingiva do we have in clinical gingival health. So we have a study from laying in low. And we'll be seeing laying in low quite a bit throughout this presentation. In 1972 they examined the width of the facial and lingual care and gingiva to determine how much current and eyes to each of us adequate for the maintenance of gingival health. They took 32 dental students, which will love to take dental students and use them for experiments and supervised hygiene for six weeks, and they assessed the buckle and lingual tooth surfaces. So basically, in conclusion, they found although surfaces may be free of detectable plaque areas with less than two millimeters of keratin ice tissue and less than one millimeter of attached gingiva were inflamed, seeing as that the movable gingival margin or the mucosa would facilitate introduction of microorganisms into the gingival crevice. So if you have more mucosa, it's really hard to brush away all of that plaque. So ideally we have two millimeters of keratin nice tissue and one millimeter of attached gingiva and gingival health. So in gingival health, you know, how often do we have to have an oral hygiene frequency? Laying in 1973 looked at the rate of plaque development and how often oral hygiene needs to be performed in order to maintain gingival health. He says. That plaque first appears on the inner proximal surfaces of the premolars, and last on the facial surfaces of the molars and the premolars. Complete plaque removal in intervals of 48 hours is compatible with gingival health, and intervals of incomplete removal of plaque greater than 48 hours resulted in gingivitis, so the key here is complete plaque removal. It's not just, you know, brushing your teeth every 48 hours. It's like which is compatible with gingival health. You have to have complete or adequate plaque removal that's not present. So probing. You know, we obviously probe every patient that comes in. So some factors that influence the probing depth are the insertion force, the size of the probe tip, the angulation and the inflammatory status of the tissues. In health we should be probing in the junctional epithelium. And we can't just use probing depth as evidence of gingival health. You know there are other factors that play a role like bleeding on probing. We have predisposing factors. We have modifying factors. And these are things we're going to go over kind of later in the presentation. But we know that the absence of gingival bleeding on probing is desirable implies a low risk of future clinical attachment loss. So keep in mind with gingival health, the absence of bleeding on probing is a reliable indicator for this. And that is another long study. So I'm kind of dove a little bit into the diagnosis of 2017 World Workshop classification. So what is clinical gingival health? Gingival health is the absence of clinical detectable inflammation. The key here is clinically detectable inflammation. And we'll talk a little bit later about why that's important. We have less than 10% of the sites are bleeding. There's no probing depths greater than four millimeters. And this can occur to a patient with an intact or a reduced periodontal. And so we can actually restore gingival health after treating a patient for gingivitis or periodontitis. So for intact periodontal and reduced periodontal. Thome I go over this a lot in the clinic with the students. So an intact periodontal has no history of periodontitis. We don't have an we have an absence of bleeding on probing erythema, edema, absence of bone loss and a reduced periodontal of a periodontitis patient. It's successfully treated in a stable periodontitis patient. So you have a history of clinical attachment loss. But now you have gingival health because the patient is stable. And you can have a reduced periodontal of a non periodontitis patient. And this is kind of where it kind of gets muddy in the clinic. So in cases of recession in crown lengthening you have clinical attachment loss. But it's not due to a periodontitis cause. So keep in mind we can have an intact periodontal with no history of periodontitis, no recession a reduced periodontal of a periodontitis patient. So a patient that had a history of periodontitis and is now stable, and then a reduced periodontal form of a non periodontitis. Someone who has a history of recession and crown lengthening so reduced periodontal. Now I'm talking a little bit about, you know, clinically absence of clinically detectable inflammation. So the gingival tissues are clinically not inflamed and healthy. They always have an evidence of an inflammatory response occurring histologically. And we call this a steady state homeostasis of low low grade inflammation. So this is referred to as physiological immune surveillance. So clinically you know we might have gingival health. It's not detectable. But histologically we are going to have some sort of inflammatory response which is associated with homeostasis. So we see inflammatory infiltrate localized to the lamina appropriate adjacent to the junctional epithelium. So key thing here like I said is healthy gingiva. We don't have or clinical gingival health. We don't have clinically detectable inflammation or gingivitis. But we do have a slight inflammatory response. So the gingiva has a lot of protective mechanisms that helps filter bacteria and the flow of different substance coming in and out. We have the maintenance of an intact epithelial barrier, the outflow of gingival fluid from the sulcus which flushes out the tissues. We have slotting of the surface epithelial cells or the junctional and cellular epithelium. We have the presence of neutrophils and macrophages to phagocytosis bacteria. And we have the presence of antibodies and the gingival fluid. So the epithelium and connective tissue are obviously very important. And the gingival epithelium connective tissue provides that physical barrier to stop the penetration of bacteria. Disruptions in this barrier can lead to further bacterial invasion and inflammation. So neutrophils are continuously migrating through the connective tissue and pass through the junctional epithelium to enter the sulcus or pocket. If a bacterial challenge persists, the cellular fluid infiltrate continues to develop, and neutrophils and other inflammatory cells occupy the inflamed gingival tissues. And I really want you to take from this is that the neutrophils are a key component of the innate immune system which you've gone over. And they play a fundamental role in maintaining periodontal health despite the challenge that is presented by plaque biofilm. And this is just another slide of the histology of the healthy gingiva. We have a photo micrograph of a mineralized tooth. We have our junctional epithelium and the a b portion. This is right over here. We have the B and C the cellular epithelium our free gingiva and our attached gingiva. And then the connective tissue is very dense and it's organized into collagen bundles. So graphically, what are we looking for when we think about clinical gingival health? In health we have an intact lamina dura. We have no evidence of bone loss in the function. Human in 1989 talked about how, you know, in two millimeters of distance from the edge to the alveolar crest is normal. So what I want you to take from this is when you look at an x ray, if you have bone loss that is 1 to 2mm from the edge to the crest, this is considered normal. Anything after that is considered bone loss. Right wing acts are very specific. So what is the bacteria associated with gingival health? So Kranti is going to come up a lot. I'm not going to go over like the red complex or orange complex, but kind of just tell you, you know what bacteria we expect to see and health gingivitis and periodontitis. The flora consists of gram positive like facultative non motile coxsackie. We have mostly strep bacteria that is in gingival health. You know, as we continue to see what a pathogenesis of disease is when we go from health to gingivitis to periodontitis, we know studies show that there is a 1 to 1 relationship between plaque formation, the development of gingivitis. One of the most famous studies is experimental gingivitis and man from low in 1965, where we kind of look at the pathogenesis of disease. So going from health to disease, after two days without oral hygiene, we had a transition of gram negative to gram negative and rods that we had a couple of days later, a future of bacteria and filaments appeared. And then several days later we have spiral sheets that are present. The conclusion is that gingivitis is diagnosed around the same time that there is a transition of more complex flora. So we have the transition of the flora, and now we're starting to see gingivitis. However, subclinical inflammation started much earlier during the first phase of plaque development. And then once oral hygiene is reinstated, most areas of inflammation disappeared in two days, and after 711 days, patients went back to similar inflammatory levels as before. They experiment. So the key here is, like I said, the transition of a more complex flora as we continue into disease. But also this also tells us that gingivitis is reversible. You know, after they restored oral hygiene procedures, everything went back to the way it was before the experiment started. So I thought this would be a kind of a nice chart for you to see the transition of gingival health to disease as we transition from a healthy status to a disease status. We see the composition of the bacterial community also changing. So this is kind of a chart I put together about health versus disease. We go from gram positive to gram negative to rods and on model to motile facultative and obligate anaerobes. So kind of keep in mind as we transition things are going to start to change. And then, like I said, more of a transition. We see negative positive rods. See. And down here this is gingival health. And then over time we have spiral sheets that form into our pockets. So the pathogenesis of gingivitis and periodontitis. Now we know what clinical gingival health is. We know how to identify it clinically. We know how to look at it on a radiograph. We know how we diagnose it. In the 2017 World Workshop classification. Now as we continue on what is abnormal, what are we looking for when we don't see normal? So there's multiple theories of pathogenesis and everything is changing all the time. So I'm sure new theories are going to come out as well. But nonspecific plaque hypothesis, specific plaque hypothesis, an ecological plaque hypothesis, or a couple of theories that have been looked at over the years about, you know, the theory of how we go from health to disease. And specifically, I know you've gone over this before, but talking about Paige and Schroeder from 1976, which is a histological histopathological roadmap of the development of detectable gingivitis, the progression of periodontitis and response to the accumulation of bacterial plaque. Like I said, now that we kind of know what gingival health is, we can kind of take what we've learned before and kind of apply it from health to gingivitis to periodontitis. So we have our initial lesion, our early lesion, our established lesion and our advanced lesion. Initial lesion 2 to 4 days after plaque accumulation. The key here is we have an increase in gingival fluid. Neutrophils and macrophages develop. And the big thing is that we can only see this lesion histologically. So there's a cellular response. But the gingiva looks healthy. In an early lesion. We developed 7 to 14 days after plaque accumulation. We have a transformation to predominantly lymphocytes and macrophages. We have proliferation. We have local collagen breakdown and vascular proliferation. And this may or may not shift into gingivitis. So that's the key from the early lesion. An established lesion 14 to 20 days, 21 days after plaque accumulation. We have the pocket epithelium is leaky. We have established gingivitis lesion. So in the initial you know we have a histological response but we can't detect it clinically in our early. It may shift to gingivitis. In our established lesion. We definitely have gingivitis. And in our last our advanced lesion. This is irreversible. This is the established periodontitis lesion. We have plaque that's further extending into the pocket. We have plasma cells predominating. And like I said irreversible clinical attachment loss. And we can have loss of connective tissue and the alveolar bone. And I really like this slide because I kind of gives a nice overview of health, gingivitis and periodontitis and how we go from health to disease. Using Paige and Schroeder to kind of understand what's going on underneath. So now that we know the health and the pathogenesis, let's kind of talk about gingivitis. So gingivitis nonspecific gingival inflammation in response to dental plaque we have erythema edema bleeding on gentle probing and pain. The key here is bleeding on gentle probing because if you probe hard enough you'll probably make the patient bleed. So key is not a lot of force when you probe. And then the clinical appearance. You know, we can get a different types of color variability with gingivitis. And this is due to the intensity of the inflammation. So we have acute inflammation that starts with erythema leading to a red color change. And then we have chronic inflammation which intensifies this red color change. And this is due to vascular proliferation. So basically what I want you to know is that the gingival color changes initially in the intra dental papilla and the gingival margin. And then kind of migrates to the attached gingiva. We can see different colors and different intensities of these colors based on the amount of inflammation that we have. So now with the gingivitis diagnosis in the 2017 World Workshop, we have two types of diagnoses. We'll mostly only talk about dental biofilm today, but there are two. So we have dental biofilm induced gingivitis and non dental plaque induced gingival diseases. So in dental plaque biofilm induced gingivitis we have an inflammatory lesion resulting from the interactions between the dental plaque and the host immune inflammatory response. This is contained within the gingiva but it can be reversed once the biofilm is removed. The non dental plaque induced gingival diseases are not caused by plaque and they don't resolve by plaque removal, although they're not caused by plaque. Plaque accumulation can increase the severity of the inflammation in these diseases, but they're mostly genetic developmental disorders, viral infections or autoimmune disorders. So then 2017 we have we can have gingivitis localized, which is less than 30% of the teeth that are affected, or generalized, which is more than 30%. Gingivitis, similar to clinical gingival health, can occur on an intact periodontal or reduced periodontal form of a non periodontitis patient and reduced. Of a periodontitis patient again reduce periodontal of a non periodontitis patient being recession history of crown lengthening among other factors and then reduce periodontal gem of a periodontitis patient. Someone who had a history of periodontitis and is now stable. Histologically, what does gingivitis look like? So we have in figure a hyperplastic junctional and cellular epithelium with inflammatory infiltrate adjacent to the connective tissue. So inflammatory infiltrate. That's right there we have inflammatory cells. And figure B at the epithelial connective tissue interface. The connective tissue is dilated. There's a lot of edema. And there's alterations in the fibroblasts and the collagen. And in figure C it's more magnification. But it's showing neutrophils and lymphocytes in the epithelium. So as you can see we kind of get more as more inflammation occurs. We have alterations of fibroblasts. We have connective tissue that's dilating. We have edema. And then we have more neutrophils and lymphocytes coming into the area. And the contents of the gingival pocket I think are really important too, is that the gingival pocket has a deepened sulcus and ulceration of the cellular epithelia and capillary dilation. Again Saransk. He's back in early stages of gingivitis. We have pro botella species. And after 14 days of gingivitis we can see other species are coming in as well. And the radiographic findings of gingivitis. This is very important is that radiographs cannot be used to diagnose gingivitis. But patients with gingivitis have, like we were talking about in gingival health, 1 to 2mm distance on average from the bone crest to the edge. This is normal. They have no evidence of bone loss in the friction areas and may present with colliculus formation visible on the radiograph. I talked to students a lot about this in the clinic, especially when they're taking their summative for their sub gingival calculus removal. Buchanan in 1987 said that calculus is only detectable on an x ray 44% of the time. So students will tell me, well, doctor, you know, I don't have to check, you know, the calculus in the mouth because I can see it on the x ray, but we only see it on the x ray 44% of the time. So detection is dependent on the thickness and the location in an x ray. And the results show that the present radiographic techniques are not appropriate for detecting calculus on the root surfaces. So the takeaway is that we all want to always check the calculus with the 1112 explorer in the mouth, because we can sometimes not see it on an x ray. I always say if you see it on the x ray, we definitely know it's there. But just because it's not on the x ray doesn't mean it's there. So what are the determinants of gingivitis. We have super gingival plaque composition and sub gingival biofilm composition. I think this is a great side because it kind of shows you the color changes that we see with different types of plaque and biofilm formation. We have in super gingival calculus. It looks very white and very chalky, especially if you like. If you dry the area and shine a nice light on it, it's really easy to see. But as we reflect a flap as we go sub gingival, we see that the calculus is actually more of a green or more of a brown color, or even a black color, and this is just due to oxidation. So when I reflect a flap I'm definitely looking for these other areas. But as well as we can usually have both supra gingival and sub gingival calculus. So know that they have different colors. So determinants of gingivitis we talked about before about predisposing factors and modifying factors. Our predisposing factors are any age and or condition that contributes to the accumulation of plaque. This is associated with both the maintenance and the severity of the gingival inflammation, and this is largely factors that are prominent with being with calculus. We have modifying factors any age or condition that alters the way in which the individual responds. So it alters the course of the inflammatory response and it alters repair potential. Some of these factors are controllable, and some of these factors are not controllable. So some of these determinants or factors or you have our dental anatomy. We have the palatal gingival groove enamel pearls crowding gingival restorations and fixed appliances. And kind of what you can see from this whole, you know, predisposing factors and dental anatomies. This is very hard to clean. You know, it's hard to get attachment with an enamel pearl. It's hard to clean teeth when there's crowding, substantial restorations. If there's an overhang, it's also very hard to clean fixed appliances, especially a fixed retainer. After orthodontic treatment or multiple bridges, they can be very difficult to clean, which is why these predisposing factors play a role in plaque accumulation or the calculus biofilm, and then modifying factors. We have hormones like puberty, pregnancy, contraceptives and things like diabetes and smoking, which we're really going to go over today as well. So some things are controllable, or some factors like removal of overhang restorations. And you can see that would definitely be a plaque trap in a patient smoking cessation. So if I have a patient that comes in to see me I always do smoking cessation. If they actually smoke. And we'll talk a little bit about how smoking plays a role in gingivitis and periodontitis, and why smoking cessation is such an important concept in parrot ontology. So we have uncontrollable factors as our genetic disposition and our immune status. So controllable, uncontrollable. So modifying factors smoking and gingivitis. So smokers and non smokers actually accumulate plaque at the same rate. So that's kind of a key point. But current cigaret smokers have a suppressed gingival inflammatory response. So nicotine causes peripheral vasoconstriction as well as a decrease in gingival curricular fluid. So thinking about that like what is the clinical significance of nicotine causing peripheral vasoconstriction? I want you to think what vasoconstriction really means. Which means that, you know, it decreases. It gets like it's very small. It comes together so clinically, basically smokers are going to have a lack of bleeding on probing in comparison to nonsmokers and gingivitis. So clinical inflammation is actually masked in smokers. So a patient might come in you might say oh well I don't see any bleeding on probing. It could be gingival health, but know that you will have a masking of the inflammatory response in smokers versus non smokers. So this is always fun. This is one of my favorite parts of the presentation. Or just, you know, I remember learning this for the first time and like I felt like my mind was blown. But, you know, in laying in 1985, evaluated bleeding on probing at maintenance visits to see if bleeding on probing sites had increased risk for periodontal breakdown. Kind of seeing like, do all gingivitis sites progress to periodontitis? And data was collected at the four recall visits. And they found that only 30% of the sites with bleeding on probing spontaneously progressed to further attachment loss. So seeing that number was kind of interesting to me because I would think that it would probably be more, but it was only 30%. So he found that bleeding on probing is a good indicator for current disease, which we talked about earlier of active inflammation, but a poor predictor for future disease. So the takeaway of this study is that not all gingivitis sites are going to progress to periodontitis. And like I was talking in gingival health, the lack of bleeding on probing is a good indicator for gingival health. But bleeding on probing is good for an active inflammation or active, a good indicator for active disease, but not for future progression of the disease. Um, and then looking at another study for this garden in 1985, they looked at 61 adults with varying degrees of gingivitis. They found only one out of a 1002. Services increased in probing depths by three millimeters or more from baseline, regardless of the recall maintenance intervals. So the takeaway from this study was that despite high levels of gingivitis, individuals were resistant to periodontitis. So now we have two studies that are kind of telling us, you know, only 30% for recall visits, only 30% of sites progressed to further clinical attachment loss. And now we have this study that's telling us, despite high levels of gingivitis and despite active inflammation and active disease, we have patients who are somewhat resistant to periodontitis. So it kind of makes you wonder, how does periodontitis progress and what other factors play a role, because it has to be more than what we're seeing. So another pretty famous study from Lowe is A Natural History of Disease and Man. It was done in 1986, and it's a study of the natural development and progression of periodontal disease. They looked at 480 male T workers from Sri Lanka from 1970 to 1985. The population did not perform any conventional oral hygiene and displayed uniform, large plaque and calculus deposits on their teeth. So what's great about this study is that it's a longitudinal study, so it's done over 15 years, which is great for data. And Lowe found that there are three types of populations that you can identify in. The rate of progression of periodontitis, which was 8%, had rapid progression of periodontal disease, 81% had moderate progression of periodontal disease, and 11% had no progression. So we're kind of thinking, okay, they all stopped their oral hygiene. You know, we don't know too much about everything else, but we know that. That they all stop. They all didn't do oral hygiene. So we have different rates of progression. And he found that the disease progression varies between individuals at different ages and within the same individual dentition. Again, it makes you wonder why does this happen? So if gingivitis always precedes periodontitis, but not all gingivitis sites progress to periodontitis. What else plays a role in disease progression? So like I said, not all sites progress at gingivitis. But we have to have gingivitis in order to have periodontitis. So the other roles that play is the immune response to the bacterial challenge of the sub. Gingival biofilm is also influenced by the host and environmental factors that affect disease progression. So what you need to have disease progression is a key thing. Here is the susceptible host. We have our systemic factors like diabetes and our environmental factors like smoking. And like I said before, patients who are smoking tend to have a mask and the inflammatory response. So lack of bleeding on probing. So what is the role of the susceptible host in the pathogenesis of disease? So the mediator of periodontal attachment loss and alveolar bone loss is the host inflammatory response that is triggered by the microbial challenge. So keep in mind you know we have this microbial challenge. And it's actually the host response that leads to this clinical attachment loss. And this alveolar bone loss. Bacteria is required to initiate periodontitis. But bacteria alone does not cause tissue destruction. So the host response has initiated against the bacteria and attacks its own tissues. So once dysregulated, the host cannot resolve the inflammation due to the microbial challenge leading to the damage of the periodontal tissues. So the host, for the most part, can actually resolve inflammation once it comes. But we get a dysregulation of this resolving of the inflammation leading to tissue destruction. Those more susceptible to the disease mount an excessive or dysregulated immune inflammatory response for a given bacterial challenge, which leads to increased tissue breakdown as compared to those individuals who have a more normal inflammatory response. So looking at the susceptible host like the risk factors, and we have our bacterial challenge and our inflammatory response or our disease threshold, you know, a certain level of bacterial challenge results in a moderate inflammatory response. So the initial response of the host is protective. And when I was talking about before, you know, we have protective mechanisms and the connective tissue and the epithelium to keep bacteria out. But if there are changes in the bacterial challenge or the host response, there can be an upregulated inflammatory response. So this related inflammatory response we can't have a resolution of inflammation. So this increased inflammatory mediators lead to tissue damage. And the threshold for an individual to transition from homeostasis to periodontitis actually happens. So once we hit that disease threshold and we keep going up you know we're going to have this dysregulated response. We're going to go from, you know, health gingivitis to periodontitis. And then this is just another way of looking at it, is that inflammatory response to a bacterial challenge. We have people who are hyper responsive to the inflammatory response and hyper responsive. So most people respond to normally to inflammatory mediators when plaque is present. Those who are hyper responsive generate an excessive inflammatory response to the same challenge, and those who are hyper responsive produce lower levels of inflammatory mediators despite the same challenge and may never progress to periodontitis. So now that we know this, the studies from before laying low with a garden, they all make sense. You know, you have to have a susceptible host. And some people are hyper responsive and some people are hyper responsive to this inflammatory response to this microbial challenge. So diabetes, we're going to be talking a little bit about diabetes and smoking later as well with the classification of periodontitis. But systemic risk factors for the pathogenesis is diabetes. And diabetics are three times more likely to have attachment loss and bone loss. And those without diabetes patients with diabetes have increased advanced glycation end products ages and receptor rage, which are further increased in periodontitis. So when a patient has hyperglycemia, there's a hyper inflammatory response. This results in increased cytokines and neutrophil defects. AGS increase inflammation by increasing pro-inflammatory cytokines, and MMP and AGS prevent development of macrophages involved in wound healing. We say this a lot, especially in the clinic. Patients who are diabetic, if they're uncontrolled, playing a role at the ages. And the macrophages, we have poor wound healing. So we want to make sure the patient has controlled diabetes before we treat because they'll have slower healing and poorer healing. We don't take this into consideration. So studies have actually shown that there is a bidirectional relationship between diabetes and periodontitis. As periodontitis can adversely affect the glycemic control and periodontal therapy can actually result in improvement of glycemic control. So kind of knowing all of this, let's look at that as a diagram. Because I love diagrams I personally very much a visual learner. So we see we have the local environment. We have increase and GSF glucose. We have salivary alterations. We have plaque biofilm dysbiosis of the pathogens. This is going to lead to inflammation cytokine imbalance, immune impairment, cellular stress now in hyperglycemia. And patients who have diabetes. We have these ages and we have oxidative stress ages born with rage. And that also leads to an inflammatory response. So we have a hyper inflammatory response now. And eventually this leads to accelerated tissue destruction and impaired wound healing leading to periodontitis. Now, the next other factor this is an environmental risk factor is smoking. And like I said, we talked a little bit about smoking and gingivitis. But now what with periodontitis. So smoking is a strong modifiable risk factor for future disease and disease progression. Smokers are two times more likely to have periodontitis than nonsmokers. Smokers also have 6 to 7 times more alveolar bone loss than those who don't smoke. Smokers have more substantial bacteria than nonsmokers, so what smoking really does is it causes an increase in pro-inflammatory cytokines responsible for alveolar bone loss and inhibits gingival fibroblasts. It decreases the revascularization of wounds. Again, poor wound healing causes abnormal chemotaxis and phagocytosis of PMS. So we have dysfunction and this leads to destruction of the periodontal tissues. So the key with smoking is that we have the inhibition of fibroblast with poor wound healing. And we have abnormal chemotaxis of our PMS which are very important. The clearance of these PMS are very important for resolution of inflammation. So now with periodontitis, I'm going to. I can keep going. Right. Yeah. Good. So I'm going to keep going if that's okay. So with periodontitis we have a chronic multifactorial inflammatory disease with this biotic plaque, biofilms characterized by progressive destruction of the two supporting apparatus. We have gingival inflammation and apical migration of the junctional epithelium or Cal clinical attachment loss. The key here with periodontitis is that we have apical migration of the junctional epithelium or the tissue. We have clinical attachment loss. And that's very important to think about because we'll talk a little bit about x rays and clinical attachment loss. So the interaction interactions between the gingival bacteria, the host's immune response and environmental modifying factors all put us into this pathogenesis from health gingivitis and to periodontitis. So features we have a loss of periodontal tissue support. We have graphically assessed alveolar bone loss. We have increased tooth mobility. The key here is increased tooth mobility. Not necessarily just tooth mobility. But we have to have an increase in this tooth mobility over time. Bleeding on probing separation which is inflammatory fluid or parole and exudate that's coming from the pocket. We'll talk about very soon. And then for patient loss the friction being the area between the multi rooted teeth. So how do we diagnose periodontitis? It's a little bit different from the 1999 classification in the clinic. You're going to be using both the 1999 and the 2017. But I tend to have more discussions about the 2017. So I thought it would be really great to put it in here. So you have a nice view of it when you do come to the clinic. And a nice and a good reference. So we have three types of periodontitis. We have periodontitis which includes the previously classified chronic periodontitis and aggressive periodontitis. And these were actually combined because treatment tends to be the same. So they couldn't find any reason to keep them separated. Periodontitis as a manifestation of systemic diseases and necrotizing periodontal diseases. We're not going to kind of go into the last two, but we'll talk a little bit about periodontitis generally. So they're further classified by less than 30% of sites is localized greater than 30 is generalized. And then we can have what we call a molar incisor pattern, which is, you know, attachment loss just at the molar or incisors versus the rest of the dentition, which kind of plays a role in what was previously classified as aggressive periodontitis. And this is a really good example of a defect that we see around a tooth. So periodontitis. How do we diagnose it now we know we can have it localized. We could have it generalized. We could have molar incisor pattern. We have three different types. We have a patient is diagnosed with periodontitis. If you know the inter dental clinical attachment loss is we have it at two non adjacent teeth or two non adjacent sites. Or we have buckle or lingual palatal clinical attachment loss of greater than three millimeters with pocketing. And observed clinical attachment loss cannot be ascribed to non periodontal causes like fracture or caries. And this is kind of where we get into this. There's a staging and our grading. But we also have something called tooth related factors or other and other category. Now whenever I tell students that they're always like of course there's another category. But we have to know that, like we can have different situations where we have clinical attachment loss, but it's not due to periodontitis. It could be it's it's periodontitis secondary to fracture or caries or clinical attachment loss secondary to this. So something to keep in mind. We won't go over this. But there is another category. And I would suggest actually reading the staging and grading on the World Workshop from 2017, because it's very interesting to see there are tooth related factors or related factors, and how this all plays a role in how we diagnose knowing that diagnosing is very important because it plays a role in how we're going to perform a comprehensive treatment plan and how we're going to treat our patients. So what is the staging? The staging? I just want you to look at it. We're not going to go through one, two, 3 or 4, but knowing that the staging is a severity or the extent of the disease that we're seeing, it's we first look at the inter dental clinical attachment loss. And then we can look at radiographic bone loss. So we have our severity. But then we have little portions of something called a complexity. So you can be in stage one or stage two and have an added complexity that pushes you to maybe a stage three. And rarely I see stage four, but also be pushed to a stage four as well. So like I said, keep in mind staging is just the severity or the extent of the disease. Then we have grading. We have the risk of progression. So staging being the extent and now grading the risk of progression. And you can kind of see how down here we have our grade modifiers or our risk factors. And there we are. Smoking and diabetes do play a role. And when we talked about wound healing. So patients you know we have grade A or slow rate usually a non smoker grade B less than ten cigarets a day. You know the amount of that you do smoke actually does play a role. And then you know the amount of glycemic control you have to. So staging the severity and grading the risk of progression of the disease. So. Clinical features of periodontitis. Separation. Purulent exudate in a periodontal pocket. It's due to the presence of neutrophils and the gingival fluid. It's formed in the inner pocket wall. It's pressure. You can you can actually see when you put pressure with a finger or a probe during your clinical examination. And I thought I would put a nice photo here. It's kind of hard to see. But you can see a little bit of inflammatory fluid. I call it inflammatory fluid to patients. I don't want to tell them that they have an exudate or like pus coming out of the pocket. I just say it's inflammatory fluid because it is you know it's like neutrophils coming out. And I especially say this when I'm probing not all sites with periodontitis have separation or exudate. And they say that only 3 to 5% of sites show signs of separation. I feel like I see separation a lot. It doesn't affect my treatment plan. It doesn't affect my diagnosis. I usually just tell students that if you see separation, you definitely have active perio, but it doesn't really change, you know, our course or our direction of the treatment. Just know that this is a factor that we can see in periodontitis. So I talk about this many, many times in one day, especially in the clinic and even outside. Outside when I'm talking to students as well, when they're not seeing a patient, we have a true pocket versus a pseudo pocket. And if you're going to take anything from today's lecture, I think this is probably one of the most important concepts. It's going to play a huge role in how you're charting patients in the clinic and how you are treatment planning. So an increased probing depth does not necessarily mean you have periodontitis. Sometimes students will come up to me and they say, well, doctor, I have four, six, seven millimeter probing depths. But and I have periodontitis. Not necessarily actually. So a deep probing depth doesn't mean you have periodontitis. In order to have periodontitis you need clinical attachment loss, which is kind of the theme of this presentation. A true pocket has a probing depth increase due to the apical migration of the junctional epithelium from its normal position at the edge, so clinical attachment loss a pseudo pocket has a probing depth increase due to coronal migration of the gingival margin. So the junctional epithelium is at its normal position at the edge. So true pocket we have the movement of the junctional epithelium from the apical migration in a pseudo pocket. Our attachment is at the level of the. So we have an increase in pocket depth due to gingival enlargement of the tissues. No loss of the supporting periodontal tissues and no loss of the connective tissue attachment. Again, I love visuals, I love a good diagram. So we have in the first diagram we have the gingival or pseudo pocket. The attachment is at the level of the edge. We see the attachment. Here we have gingival enlargement. We have. That's due to coronal migration. The gingival margin from the sulcus base. We have periodontal pocket which is the pocket depth is increasing due to the apical migration of the junctional epithelium from its normal position at the edge. So the attachment is apical. So you can have a seven millimeter pocket. And it could be a pseudo pocket. And it could or it could be a true pocket. And then you know in the clinic will teach you how to kind of determine, you know, where when we have a pseudo pocket versus when we have a true pocket. But knowing that in a pseudo pocket we don't have a migration of the attachment and a true pocket we do. So periodontitis, the true pocket can actually be defined into even more subcategories. We have a super bony pocket. So the sulcus space is coronal to the alveolar crest. The pocket wall lies coronal to the bone. And the bone loss is always horizontal. So you can kind of see in this photo right on the bottom right there you have your sulcus base is more coronal to the bone and an infra bony pocket. We have the sulcus spaces apical to the alveolar crest. So below the bone. And the pocket wall lies between the tooth and the bone. And bone loss is mostly vertical. So like I said keep in mind we have two different classifications of periodontitis. We have our super bony pocket and our inner bony pocket. So the development of the periodontal pocket, you know, early stages of pocket formation. We have the detachment of the cells at the coronal portion of the junctional epithelium. The cells at the apical aspect of the junctional epithelium are going to start to migrate. At the same time we have epithelial cells. They don't have their own blood supply. So they depend on nutrients from the surrounding connective tissues. So as we have this epithelium that's proliferating and apical migration the cells that are more coronal. Does the connective tissue actually start to necrosis. And we get intra epithelial clefts. So the immune response in a periodontal pocket. You know, patients with periodontitis have hyperactive neutrophils. They have overproduction of damaging damaging Ros which is reactive. Oxidative species degradation of the fibroblasts limits repair. Again keeping in mind fibroblasts play a huge role in wound healing. And that helium continues to proliferate apical so the connective tissue is starting to degrade. This is by amps produced by fibroblasts and micro macrophages. We have greater collagen activity in periodontitis. And then we have extracellular release of lysosomal enzymes, which contributes to the continued tissue damage and collagen depletion in the periodontal tissues. So the root surface. I think this is actually a great slide too, because it's not just the pocket that is actually changing the route. Wall surface is also changing, and the route service well changes significantly during pocket formation. We have as the pocket increases, collagen fibers and cement them are destroyed. The explosive momentum and the remnants of the sharpest fibers degrade and create a favorable favorable environment for bacteria to penetrate. Bacterial products like endotoxins have been detected on cement, and clinically, this momentum is very soft and it's usually asymptomatic unless it's probed. So exposure of this route symptom or this root surface wall to bacteria and the oral cavity can lead to cavitation, root carries and dentin hypersensitivity. Most of the time when my patients are having dentin hypersensitivity, it's usually more of a cold response or like an air response. So not so much a hot response. And then periodontitis. You know, the periodontal pocket content. And now that we see changes in the junctional epithelium the connective tissue we see changes in the root wall surface. We have the contents of the periodontal pocket which is debris of microorganisms and their end products. We have gingival fluid. We have food remnants salivary mucin. We have disc dominated epithelial cells leukocytes and separation or Paru and exudate like we talked about before. Histologically, though, what does this look like? And now that we know the histology of health and gingivitis, now we can look up periodontitis. So this is an a staining of a periodontal pocket. So we have actually two teeth. This is one tooth. And we're actually looking at this tooth all the way over here. We have a the tooth the right to this covered in a layer or I guess it's your right my left. But it's covered in a layer of plaque. So we can see actually this is all plaque here. P is the actual periodontal pocket. And we see that the base of the pocket or BP is lower than the entire dental bone. So we have the base of the pocket is apical to the alveolar bone crest. And a b is actually just the alveolar bone. So we can actually see histologically what this pocketing is starting to look like. So disease activity. Remember how I kind of talked about how there's different theories of disease progression? Well, here's another one. This is probably one of the most important ones you will learn. It's used to be thought that a loss of attachment was due to the slow but continuous disease progression. So Krinsky again, you know, showed that the periodontal pockets actually go through periods of exacerbation. So activity and inactivity and episodic bursts of activity. So we have during these inactive bursts or inactive time we have reduced inflammatory response and little to no connective tissue or bone loss. Plaque will start a period of exacerbation where connective tissue and bone are loss depending on deepening the pocket. So this can last days. This can last weeks. This is followed by periods of remission. So sequencing in 1984 is looking a lot about, you know, bursts of activity and periods of remission saying that it's not really a slow but continuous disease progression. But we have, you know, periods of activity and inactivity that could last from days, weeks to months. So we have activity followed by inactivity and then again. Bacteria and periodontitis. The three main, you know, controllers or people or people or bacteria that play a role in periodontitis. Gingivitis. Two. Forsythia. Tentacles. We have our orange complex as well. And then I added this in here the aggressive or molar incisor pattern. We tend to have a that plays a role against the Kerensky. We have our red orange green and yellow complex. Seeing how there's an interplay of bacteria and as pocket depth increases we have a change in the bacteria. If we look at the experimental gingivitis study from low, as we see that we have a transition from health to disease of the flora of bacteria. The same is to be said about gingivitis into periodontitis as well. And this is a great chart. I think about, you know, the pathogens in health versus periodontitis. We see that we have an increase in health of gingivitis about 10% to about 60%. You see that we have this kind of change in the flora as we continue from health, gingivitis and periodontitis. So periodontitis we have patterns of bone destruction. So like I said you know we have clinical attachment loss. But we could also have alveolar bone loss as the gingival inflammatory infiltrates spreads through the blood vessels and into the bone. It also goes into the marrow spaces as well. So the bone marrow starts to become replaced with this leukocyte exudate and perforating fibroblasts. So this inflammatory infiltrate is going to start to replace the bone marrow. Phagocytes and osteoclasts are now going to increase in number in the bone surface. We know that phagocytes play a role and phagocytosis and clearance and osteoclasts play a role in bone loss or resorption. Bone resorption continues from within the bone, causing it to thin and enlarging the marrow space. So the key point of this slide I want you to think about with periodontitis is bone. The bone loss that we see is not due to the necrosis of the bone. The bone is still living, the cells are still living, but we have a bone. Loss occurs due to the activity of the living cells within the bone. The bone marrow is being replaced by inflammatory infiltrate. We're having resorption of the bone. So the bone is still living. It's not necrosis when we have periodontitis. So how does this occur. And this is where our inflammatory factors are going to kind of come in. We have rank and rank L. So bone turnover is controlled by the receptor activator nuclear factor B in this rank rank ligand osteo progesterone OPG system. And I know that's a lot of words and it's a lot of scientific abbreviations. But we're going to kind of go through step by step. So rank L is a ligand. And this binds to its receptor rank. This rank receptor is on bone marrow stromal cells osteoblasts and fibroblasts. So the binding of rank L or the ligand to its receptor rank results in osteoclasts differentiation and activation, leading to bone resorption. So the easy way of looking at it is rank L combined with rank leads to bone resorption. When OPG binds to rank, which is produced by bone marrow and stromal cells, osteoblasts, and fibroblasts. We actually have, you know, a decrease in bone resorption. So rank and rank L and OPG are both cytokines. They both bind to rank and they result in different cellular processes. Rank L promotes activation differentiation of osteoclasts. But OPG has the opposite effect and instead inhibits the differentiation of osteoclasts. So the balance between OPG and rank L activity drives bone resorption and bone formation. So that's how we kind of get the patterns of bone loss and the pathogenesis of alveolar bone loss and periodontitis. Is our rank rank L and OPG you know connections. And if we look at it from, you know, a like a chart view, we can see that we have rank our receptor osteoclasts precursors, we have rank L and we have OPG rank can the receptor will bind to OPG or rank L. And so knowing that when we have rank L is higher there is more bone resorption. When OPG is higher, there will be more bone formation. And, you know, inflammatory mediators or cytokines like IL one B and TNF alpha regulate the expression of rank. And OPG and T cells also expressed rank. So kind of looking at all the different markers that you learned about and kind of putting it together and how it plays a role in bone loss and the progression of disease. So periodontitis. We have osteo class. And I know you all have already seen osteoclasts, maybe microbiology and anatomy, but we can actually stain for for osteoclasts in histology using what we call trap. Osteoclasts are multi nucleated. And we see when we see them we have like a nice ruffled border knowing that we have or having bone resorption. So now that we know kind of what happens underneath, we have bone loss. We have rank L and OPG. We have rank the receptor. Now what happens clinically. What do we see on an X-ray. What do we see when we see a patient. How do we interpret the findings that we have with our probing depths and our radiographs. So radiographs are great. They show existing bone volume. They assess bone loss infarction areas. We assess calculus and decay and restoration. So we can see those overhang restorations which are predisposing factors that play a role. And you know plaque accumulation. We're looking at decay. You know decay has tons of bacteria and demoralize a tooth. And calculus as we know, we're not always going to see it on an x ray. But if we have it on an x ray, we definitely know it's there. And then assessing, you know, bone loss and the friction areas. However, this is a key thing to take in mind and keep in mind and why I always talk to students about this all the time as well. Periodontitis definition is clinical attachment loss and not necessarily just alveolar bone loss, because in early stages we actually do not really see bone loss on an x ray, and radiographs may underestimate the extent of the bone loss and milder case as an overestimate it in more severe cases. And x rays don't show you the current disease activity, but they just show you the existing bone volume. Well, it's great to see the existing bone volume. We really don't know what's going on underneath or the changes that are coming on underneath based on looking at the x ray. And sometimes, you know, actually, for the most part, clinical attachment loss precedes radiographic evidence of bone loss by 6 to 8 months. So I always tell students, you know, the kind of the key takeaway is just because we don't have bone loss on an x ray doesn't mean we don't have periodontitis. We need clinical attachment loss. And a lot of times it's clinical attachment loss. These deeper probing depths with, you know, a clinical attachment loss starts about 6 to 8 months before. So you can have clinical attachment loss without radiographic bone loss. So we can't help diagnose soft tissue pseudo pockets or clinical attachment loss with the radiograph. But the radiograph can tell us a little bit about vacation loss remodeling. If it's fuzzy. And we'll go. And existing bone volume will kind of go into the different ways we can look at radiographs from here. So how does bone bone happen? How does bone loss and patterns of bone destruction play a role? So factors that determine the morphology of the bone defect. So there has to be a factor. You know again we think about why our patients are more susceptible than others to bone loss or clinical attachment loss. There has to be other factors. So we have the thickness of the entire dental septa, the thickness of the facial and lingual alveolar plates. We have the presence of fenestration and distances. We have root position within the alveolar process, root anatomy and root trunk anatomy, and root proximity. So all of these play a role in bone loss. So a distance versus a situation. So a distance is a denuded area of the bone covering the two routes. I like to look at it as a door. If you open up a door you know you have a large rectangular space. Kind of looking at you. And an offender station is an isolated area in which the root is denuded of the bone. And I look at this as a window because we still have some a little bit more bone below, but it's more of like in the middle, like as if you're like looking out the window of a house. So we have our distance and fenestration and these are kind of hard to tell. You can't really it's hard to tell on a radiograph. It's not. Sometimes it's not until I actually reflect a flap that I can I can see if initiation or a descent. So radiographic bone loss. We have different types of bone loss. We can see on an x ray. So the features of radiographic bone loss we have a fuzziness or a break in the lamina dura. We have an intact lamina dura usually indicates periodontal health. We can have a wedge shaped radial loose and see on the medial or distal aspect of the crest. We can have inter dental bone loss and reduction of the inter dental septum. And then we can have a radial loose and see at the function. So looking right here we see that there's a little there's a radial licensee around the function area. So we have some vacation loss we have and the intercept inter dental bone. We have a little bit of fuzziness which can show remodeling of the bone that there is bone loss. And then below we can see horizontal alveolar bone loss which we're going to talk a little bit about more the next coming slides. So the progression of alveolar ridge loss. It could be quite significant. And I thought this was a great slide to show about like the mandibular anterior incisors, the same ones. Over the course of time. We can see the start of of bone loss here. And as we continue, we have a progression of horizontal alveolar bone loss as we continue. So CBC TV, I talked to, you know, students and even patients all the time. And even actually I work in a periodontal office. So I have a lot of general practitioners who refer to me, and they're always asking me to take a CBC for any vacation involvement for suspected root fracture. And just overall, you know, and I always have this conversation with them is that, you know, the AAP says there's limited evidence supporting the utilization of CBC for the diagnosis of intra bony infarction defects. And there's just no current evidence based guidelines on its need f