Endothelium, plaque rupture and vascular injury Flashcards
What is endothelium?
- Tissue consisiting of a single layer of cells that lines the blood and lymph vessels, heart, and some other cavities
- Arteries vs capillaries vs veins vs lymphatics
What are the tissues present in the Tunica Intima?
Tunica intima = endothelium + thin layer of connective tissue (CT)
What are the layers of tissue present in the Tunica Media?
- Tunica Media = vascular smooth muscle and connective tissue
What layers of tissue are present in Tunica Adventitia?
Adventitia = loose CT
In a very BROAD sense what is the difference between large arteries, smaller arteries, and arterioles?
- Large Arteries - more elastin
- Small Arteries - more collagen
- Arterioles - more smooth muscle
What is the effect of inflammatory activation on endothelial and smooth muscle cells?
- Inflammatory activation of these vascular cells corrupts their normal functions and favors proartherogenic mechanisms that drive plaque development
What was the first gas to be discovered as a signaling molecule in the body?
Nitric Oxide (NO)
What is Nitric Oxide’s role in the body?
-
cGMP-mediated vasodilation
- Expressed on luminal side of endothelium
- Made by NO Synthase (enzyme catalyst)
- Come from L-Arginine
What are the 3 main inflamatory molecules that promote an “inflammatory state” in the endothelium?
- Selectins
- Cell Adhesion Molecules (CAM)
- Cytokines
Describe the formation of an atheroscleoritc plaque begining from a monocyte
Hint - Monocyte is the first step
*see attached image for more detailed depiction
Monocytes -> Macrophages -> Foam Cells -> SM cell activation / migration ->
- Apoptosis
- Fibrosis
- Ongoing inflammation
What are the 3 steps of atheroscleoritc plaque progression?
- Fatty Streak formation
- Endothelial dysfunction
- Lipoprotein entry/modification
- Leukocyte recruitment
- Foam cell formation
- Plaque Progression
- SM cell migration & inflammatory state
- Plaque disruption/rupture (unstable plaque)
- Thrombus formation
What are the features of a stable plaque?
Stable Plaques
- Rich in fibrous tissue
- Calcified
- Less lipid content
- Less inflammation
- Less apoptosis
What are the features of vulenrable plaques?
Vulnerable Plaques
- Less fibrous tissue
- Less calcified
- More lipid content
- More inflammation
- More apoptosis
Why do we care about vulnerable vs stable plaques?
Vulenrable plaques rupture, thrombose and lead to clinical events
- e.g. - leads to MI
What molecules regulate thrombosis?
- Heparin sulfate/thrombin - surface of endothelium
- NO / platelet activation - secreted by endothelium
- Prostacyclin - secreted by endothelium
What are the 5 main risk factors for atherosclerosis?
- HTN
- HLD (hyperlipidemia)
- Smoking
- Diabetes
- Age
What are the 5 different mechanisms of ischemia?
See attached
- Narrowing of vessel by fibrous plaque
- Plaque ulceration or rupture
- Intraplaque hemorrhage
- Peripheral emboli
- Weakening of vessel wall
What are the 2 common mechanism of stroke?
Atheroembolization from carotid bifurcation lesion
- Source lesion does not need to be obstructive (<70% diameter reduction)
- Ophthalmic artery
Thromboembolization from left atrial appendage in setting of atrial fibrillation
- MI and stable angina are both manifestations of what?
- What are the pathologies of MI and stable angina?
- Coronary Artery Disease (CAD)
- MI has a different vascular pathology vs angina
- MI – ruptured plaque, in-situ thrombosis, not necessarily obstructive prior to rupture
- Angina - stable, obstructive (>70% diameter reduction) lesion
Describe the progression of a Myocardial Infarction?
Not all the same severity
- Plaque rupture-> non-occlusive thrombosis -> some flow but intermittent occlusion or embolization -> stabilize with anticoagulation / vasodilators
- Plaque rupture -> occlusive thrombus -> no flow -> clinical emergency -> recanalize
What are two manifestations of Peripheral Arterial Disease (PAD)?
- Claudication
- obstructive, stable plaque)
- Acute Limb Ischemia
- Acute event obstructs blood flow without prior development of collaterals (anastomosis)
What is the difference between a stable plaque and an unstable/vulnerable plaque?
**Likely a test question, make sure you know this**
-
Stable plaques
- Less biologically active
- Cause angina and claudication (exertional ischemia) if obstructive (>70% diameter reduction)
- Less likely to cause thrombotic and embolic events
-
Unstable / Vulnerable plaques
- More biologically active
- Cause MI and stroke
- More likely via thrombotic and embolic mechanisms
What is Venous Thomboembolic Disease (VTD)?
Includes: Deep Vein Thrombosis (DVT) & Pulmonary Embolism (PE)
Venous thrombosis is different than arterial thrombosis
What are the characterisitcs of a venous thrombosis?
**Likely more background than memorization**
Venous Thrombosis
- Fibrin rich
- Have lots of RBC
- Occur in areas of stasis
- Often involve genetic/environemental predisposition
- Treated with anticoagulation
What are characteristics of arterial thrombosis?
**Likely more background than memorization**
Arterial Thrombosis
- Platelet rich
- Occur due to plaque rupture
- Occur in areas of high flow
- Result in atherosclerosis, trauma, APLA
- Treatment focus more on antiplatelet therapy
What is a Vasospastic Disorder?
Vasospastic Disorder
- Dysfunctional endothelium involved but not necessarily resulting inthrombosis or atherosclerosis, just vasospasm
What 3 things does a healthy endothelium help control?
Healthy endothelium helps reduce/control:
- Inflammation
- Thrombosis
- Vasospasm
Did you know that there are 12 practice questions at the end of this lecutre included in the powerpoint? Link is on the backside of the card if you are interested.
Questions are at the end of the Powerpoint
