6. Periodontal-Systemic Relationships Flashcards
How Dose Systemic Diseases Influence Periodontitis?
This is a very important picture. It gives an overview of how periodontal disease starts.
You need to have bacteria first (or virus) but mainly ____. Bacteria have antigens and byproducts (LPS) that trigger ____ system.
The second part is the host immune system. This contributes to future disease breakdown.
When bacteria attacks host, the host will have ____ or ____ and ____ immune system to fight bacteria. The host tries to protect itself, but PMNs also release cytokines and mediators of inflammation that traumatize the tissue and cause connective tissue breakdown. [For example] ____ is mainly secreted by neutrophil that can be detrimental for the host itself. This ____ break down eventually leads to periodontitis.
But for today, I am only going to focus on the yellow boxes. I am going to talk about these risk factors and how they affect host immune system and inflammatory status.
bacteria
host immune
antibody innate adaptive MMP tissue
WE KNOW THAT…
Systemic conditions and diseases can affect ____ (e.g. HIV, Down syndrome, immune disorders, diabetes, malnutrition etc)
WE DO NOT KNOW AS MUCH…
The consequences of diseased periodontium on ____ health
Immune system affects periodontal disease. If you have ____, your periodontal disease will get worse. We will talk a lot about diabetes today. All of these factors will influence periodontal disease.
However, we don’t know how periodontitis influences ____ health. This is a hot topic of research right now.
periodontium
systemic
HIV
systemic
Systemic Diseases Chronic Periodontitis Has Been Linked to
* \_\_\_\_ is most important * \_\_\_\_ is the common factor among all diseases including periodontitis
[READ ALL OF THESE!!]
diabetes
inflammation
How Did It all Start?
• ____ infection theory: a pathological process, in any given body site, can be the cause of the beginning or setting of a new pathology in a different part of the body of same individual (William Hunter 1910)
In 1940s and 50s, this theory fell out of fashion due to lack of ____
Late 1980’s
Theory has been ____
Possible relationship between ____ infection
and ____ disorder
• Bacteria in mouth will spread via \_\_\_\_ and reach distant organ
focal evidence revived oral systemic circulation
How Periodontal Disease Could Contribute to Systemic Disease?
Direct mechanism (____) : As chronic periodontitis progresses, the epithelium lining periodontal pockets becomes ____ providing a direct entry point for periodontal ____ into the systemic circulation. The circulating bacteria could then have direct effects on certain organs
Indirect mechanism (____): The inflammatory response to periodontal bacteria or their by-products may have indirect systemic effects. It is now well recognized that inflammation itself is involved in the pathogenesis of many chronic illnesses such as ____ disease, ____, and ____
Indirect
- This is related to inflammation. Bacteria cause local inflammation. ____ are
secreted to the local area. The mediators will also travel thru body and cause more systemic inflammation.
infection
ulcerated
bacteria
inflammation
cardiovascular
type 2 diabetes
rheumatoid arthritis
cytokines
Subgingival Environment as a Reservoir for Bacteria
The periodontium may serve as a ____ of bacteria, bacterial products, and inflammatory and immune mediators which can interact with other organs, increasing the risk for certain conditions by contributing to disease pathogenesis
Pocket epithelium in contact with biofilms in a patient with moderate to severe periodontitis = ____ of palm
reservoir
size
Periodontitis Associated Systemic Disease
Direct
- You can also see biofilm is in subgingival area, and pass thru junctional pocket
epithelium and spread out. This is the direct pathway. It can go to the heart and cause ____.
- It can also go to uterus and placental membrane and cause ____ birth.
- When we swallow oral bacteria, we can cause ____ in the gut. There may be an association here with ____ cancer based on some research I did at Columbia.
Indirect
- You can see how the byproduct like TNF, IL1B, IL6 will cause ____ phase response in liver. This severe ____ will help progression of the ____ disease and ____ birth I just mentioned.
artherosclerosis
preterm
dysbiosis
colon
acute
inflammation
heart
pre-erm
Difficulties - Confounding and Causality
Confounding: The risk factors for many systemic diseases overlap with those associated with periodontitis such as ____, gender, ____, obesity, ____ status, etc.
Cause and effect relationships
Cause and effect
- In a study, you need to have a strict ____ sequence to determine which disease
happened first. You also need a ____ study to see if the other disease increased.
You can also use ____ trials. For example if you treat periodontitis, will that help blood sugar control in diabetes patients?
age
smoking
socio-economic
temporal
longitudinal
interventional
Background Information
Diabetes is a complex metabolic disorder characterized by chronic ____
Prevalence: ____ of the US population
Blood sugar levels are regulated by a hormone called ____ that is synthesized by ____ cells of the ____
Clinical symptoms of DM
____, polydipsia, ____, pruritus, weakness, ____
Complications: microvascular diseases (____, nephropathy, neuropathy), macrovascular diseases (____, cerebrovascular conditions), impaired ____, increased susceptibility to infections
Treatment goal – reduce blood ____ levels to prevent complications
• Sixth complication of diabetes: \_\_\_\_
hyperglycemia 8.3% insulin beta pancreas
polyuria
polyphagia
fatigue
retinopathy cardiovascular wound healing glucose periodontitis
When you eat food, it will break down in blood to cause elevated ____. The pancreas secretes insulin and then the ____ will be transported into muscle and other cells to be used as energy. Insulin also help store excess glucose as ____ in muscle and liver. Insulin also help ____ breaking down glycogen to glucose in the blood.
blood glucose
glucose
glycogen
prevent
Primary Diabetes
• Type 1 (5-10%): impaired production of insulin (insulin ____)
- ____ autoimmune disease
- Destruction of insulin-producing ____ cells of pancreas (viral
infection in predisposed individuals /autoimmune response)
- 90% diagnosed before age ____
• Type 2 (90-95%): deficient utilization of insulin (insulin ____)
- Disorder of ____ immune system or results from a ____
inflammatory process
- Changes in the structure or number of the cell ____ for
insulin, or defects of the insulin-signaling ____
- More gradual and less ____
- Usually present after age ____
• Type 3 - related to \_\_\_\_
dependent
beta
21
resistance innate chronic receptors cascade severe 40
alzheimer’s
Secondary Diabetes
Hyperglycemia secondary to other diseases or conditions
- –____ diabetes associated with pregnancy
- —–2% to 10% of all pregnancies but disappears after ____
- —–Mainly in the ____ trimester
Associated with diseases that involve the pancreas and the destruction of the insulin-producing cells
——Endocrine diseases (e.g., ____, ____ syndrome), tumors, ____, and drugs or chemicals that cause altered ____ levels
gestational
delivery
third
acromegaly
cushing’s
pancreatectomy
insulin
Usually only type 2 and gestational relates to ____ . For type 1, you need insulin ____ to treat.
For type 2, you usual ____ medicine to treat. For Gestational, this is similar to type 2.
You can also use diet and lifestyle change for ____ to get a better results. Also there is a ____ for type 2 and gestational, whereas type 1 is usually ____ .
overweight
injection
oral
type 2
family history
random
Diagnosis of Diabetes
These are different blood glucose tests - A1C
○ Glucose ____ bind to Hemoglobin
○ Looks at blood sugar of past 3 months, because ____ turnover over every 120 days
○ Normal: below ____ // if over 6.5 = ____
- Random plasma glucose cell
○ If patient has more than ____ = diabetes - Fasting plasma glucose
○ Patient fast for 8 hrs and you test if more than ____, you have diabetes. -
Oral glucose tolerance test
○ [audience answer]: give a patient ____, and you test their blood glucose levels later to see how it is dealt with
○ We usually use this for ____ patients for ____ diabetes
irreversibly
RBC
5.7
diabeters
200
126
glucose dosage
pregnant
gestational
How Does DM Affect Periodontitis?
Possible mechanism influenced by ____
Alteration of bacterial pathogens
To date, there is insufficient evidence to support the role of a specific altered ____ that is responsible for periodontal disease destruction in patients with diabetes
Polymorphonuclear Leukocyte dysfunction
In patients with poorly controlled diabetes, the function of PMNs, monocytes, and macrophages is ____
-Altered Collagen Metabolism
Excessive ____ and its receptor ____ formation
The interaction leads to immune cell ____ and increased ____ cytokines
• Advanced glycation end product** + RAGE > immune cell dysfunction and increase pro-inflam cytokine
hyperglycemia microflora impaired AGEs (advanced glycation end-products) RAGEs dysfunction proinflammatory
AGEs (Advanced Glycation End-Products) & RAGEs
Monocytes, macrophages, endothelial cells have increased receptors for ____
Binding of AGE to its receptor (RAGE) results in the upregulated production of ____ mediators such as IL-1β, TNF-α and IL-6
AGEs also enhance the ____ (rapid release of ROS) in PMNs, which has the potential to significantly increase local ____ damage in periodontitis
AGEs accumulation affects the ____ and ____ activity of mononuclear and polymorphonuclear phagocytic cells due to vascular occlusion resulting from the ____ endothelial basement membrane
AGEs have detrimental effects on ____ metabolism, leading to impaired repair and bone formation and decreased extracellular matrix production
AGEs (RAGEs)
inflammatory
respiratory burst
tissue
migration
phagocytic
thickened
bone
- AGE used to crosslink ____, but too much > the collagen cannot turnover to ____ - more susceptible to infection and impaired wound healing
- Causes ____
- Influences ____ via turnover rate
collagen
repair
vascular occlusion
wound healing
Network of Potential Mechanisms Involved in the Pathogenesis of Periodontitis in Diabetes
• AGE/RAGE axis, influences \_\_\_\_ dysfunction and \_\_\_\_, eventually traumatizing \_\_\_\_
dysfunction
inflammation
periodontitis
How Does Periodontitis Affect DM?
- Periodontitis contributes to ____
- – Elevated serum ____ (IL6, TNFalpha and C-reactive protein (CRP))
- Increase insulin ____
- – TNF-alpha, IL6, CRP have been shown to impair intracellular ____ signaling, potentially contributing to insulin resistance
- Periodontitis increases ____
- – Systemic dissemination of these periodontal organisms or their products may induce a ____ or ____, inducing an elevated ____ state and stimulating increased levels of ____ inflammatory markers
- Periodontitis increasing bacteremia = ____
- (Inflammation is ____)
inflammation
proinflam cytokines
resistance
insulin
bacteremia bacteremia endotoxemia inflammatory serum
Periodontal Disease -> Diabetes Mellitus
Periodontal pathogens will cause insulin ____ which leads to ____. The pathogen will also release ____ (LPS), which triggers ____ cytokines that is usually localized first and then spreads out to cause systemic ____.
resistance
hyperglycemia
endotoxin
diabetes
Two Way Relationship
It is a ____ relationship between diabetes and periodontitis.
The heart of this relationship is ____. There are many different diseases but conclusion is all the same: inflammation. This is related to ____ of inflammation.
Hyperglycemia cause ____, alter PMN function (cannot fight bacteria –> more severe periodontitis), alter ____ for matrix formation cells (prevents repair)
____ - another main focus of this lecture that cause periodontitis.
bi-directional
inflammation
dysregulation
AGE/RAGE
apoptosis
smoking
Is Having Diabetes a Risk Factor for Periodontal Disease?
The majority of well-controlled studies show a higher ____ and severity of periodontal disease in individuals with diabetes as compared with nondiabetic persons with similar local factors
It was found that the average pocket depth as well as the clinical attachment loss was ____ in patients with diabetes mellitus (____ of the type of diabetes mellitus)
Adult who are 45 years old or older with poorly controlled diabetes (i.e., with a glycated hemoglobin level of > ____) were ____ times more likely to have severe periodontitis than those without diabetes. The likelihood was even greater (____ times) among ____ with poorly controlled diabetes
prevalence
increased
independent
9%
2.9
3.6
smokers
